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University of Texas Southwestern Medical Center
1.
Chen, Jian.
Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells.
Degree: 2011, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/938 
► Malignant glioma is one of the most aggressive cancers. To study the biology of glioma, our lab previously developed a series of mouse models that…
(more)
▼ Malignant glioma is one of the most aggressive cancers. To study the biology of glioma, our lab previously developed a series of mouse models that phenocopy both tumor initiation and progression through stochastic tumor suppressor loss-of-heterozygosity (LOH). To determine whether the mouse models recapitulate human glioma at the molecular level, we have performed gene set enrichment analysis (GSEA) comparing the molecular signature of tumors that develop in our mouse glioma models to the gene expression profiles of a number of human tumors. Our mouse glioma models share high similarity with human GBM and showed a generally proneural marker gene expression profile. We also found that tumors from the same initial genetic mutations can be further divided into several subtypes.
Previous studies suggested a neural
stem/progenitor cell (NSC) origin for gliomas, however strict exprimental evidence was still lacking. To examine the role of NSCs in glioma, we developed an NSC-specific tamoxifen-inducible nestin-cre driver mouse. When crossed to the NF/p53/Pten flox mice and induced with tamoxifen at E13.5, the Nes-Cre;Nf/p53/Pten mutant mice exhibited tumor initiation and progression similar to our previous mouse model using hGFAP-cre, with complete penetrance. All analyzed mice that were induced at 4 weeks such that only
adult neural
stem cells were targeted, developed malignant astrocytoma 7 - 12 months after induction. These findings indicate that despite their rarity, neural
stem/progenitor
cells are sufficient targets for the accumulation of mutations that initiate malignant astrocytomas.
Our highly physiological relevant mouse model also allowed us to address the question of how glioma is maintained in vivo: whether tumors are maintained by a subpopulation of
cells with self-renewal capacity that supplies tumor bulk, or whether the majority of tumor
cells have the capacity to maintain the tumor. In our spontaneous somatic mouse model of glioma, a Nestin-¦¤TK-IRES-GFP transgene labels the primary tumor
cells that are required for tumorigenicity in allograft assays. Ablating endogenous Nes-¦¤TK-positive
cells significantly extended the survival of tumor-bearing mice by decreasing tumor proliferation and infiltration. We show that the glioma drug, temozolomide, selectively targets endogenous CSC-derived proliferating
cells. Furthermore, a combination therapy targeting both dividing
cells and the CSCs arrests tumor progression.
Advisors/Committee Members: Parada, Luis F..
Subjects/Keywords: Gliomas; Adult Stem Cells; Tamoxifen
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APA (6th Edition):
Chen, J. (2011). Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/938
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chen, Jian. “Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/938.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chen, Jian. “Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells.” 2011. Web. 07 Mar 2021.
Vancouver:
Chen J. Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/938.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chen J. Malignant Gliomas Originate From Neural Stem/Progenitor Cells and Are Maintained By Cancer Stem Cells. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/938
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Urbana-Champaign
2.
Miller, Claire.
An insulin-like peptide regulates size and adult stem cells in planarians.
Degree: PhD, 0323, 2012, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/29421
► Animal growth depends on nutritional intake during development. In many animals, nutritional status is uncoupled from moderation of adult stature after adult size is achieved.…
(more)
▼ Animal growth depends on nutritional intake during development. In many animals, nutritional status is uncoupled from moderation of
adult stature after
adult size is achieved. However, some long-lived animals continue to regulate
adult size and fertility in a nutrition-dependent manner. For example, the regenerating flatworm Schmidtea mediterranea becomes smaller, or degrows, during periods of starvation. These animals provide an opportunity to readily observe
adult stem cell population dynamics in response to nutritional cues. We explore the role of insulin signaling in S. mediterranea. We disrupt insulin signaling via RNA interference and show that animals, despite eating, degrow similarly to starved animals. Utilizing in situ hybridization and immunofluorescence, we assess cellular changes in proliferative populations including the planarian
adult stem cell population (neoblasts) and the germline. Both impaired insulin signaling and nutritional deprivation correlate with decreased neoblast proliferation. Additionally, insulin signaling plays a role in supporting spermatogenesis that is distinct from the effects of starvation. In sum, we demonstrate that insulin signaling is responsible for regulation of
adult animal size and tissue homeostasis in an organism with plastic
adult size. Importantly, insulin signaling continues to affect
stem cell and germline populations in a mature organism. Furthermore, we show that
adult organisms can differentially regulate specific cell populations as a result of environmental challenges.
Advisors/Committee Members: Newmark, Phillip A. (advisor), Newmark, Phillip A. (committee member), Ceman, Stephanie S. (committee member), Raetzman, Lori T. (committee member).
Subjects/Keywords: Planarians; Insulin; Adult Stem Cells
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APA (6th Edition):
Miller, C. (2012). An insulin-like peptide regulates size and adult stem cells in planarians. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/29421
Chicago Manual of Style (16th Edition):
Miller, Claire. “An insulin-like peptide regulates size and adult stem cells in planarians.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed March 07, 2021.
http://hdl.handle.net/2142/29421.
MLA Handbook (7th Edition):
Miller, Claire. “An insulin-like peptide regulates size and adult stem cells in planarians.” 2012. Web. 07 Mar 2021.
Vancouver:
Miller C. An insulin-like peptide regulates size and adult stem cells in planarians. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2142/29421.
Council of Science Editors:
Miller C. An insulin-like peptide regulates size and adult stem cells in planarians. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/29421
Louisiana State University
3.
Addison, Meredith Kathleen.
Lentiviral transduction of epigenetically modified bovine adult stem cells.
Degree: MS, Animal Sciences, 2012, Louisiana State University
URL: etd-07162012-103728
;
https://digitalcommons.lsu.edu/gradschool_theses/4024
► Bovine adipose-derived stem cells (ADS), a form of adult stem cells, are somatic cells that have similar characteristics of embryonic stem (ES) cells. Bovine ADS…
(more)
▼ Bovine adipose-derived stem cells (ADS), a form of adult stem cells, are somatic cells that have similar characteristics of embryonic stem (ES) cells. Bovine ADS cells possess multipotent capabilities and have been found to express pluripotency genes associated with ES cells. The unique properties of ADS cells make them a desirable source for reprogramming experiments. The goal of reprogramming experiments is to transform somatic cells from a differentiated state to a pluripotent state. When somatic cells reprogram, there are certain epigenetic changes or modifications that must occur in order to successfully reprogram the nucleus. Epigenetic modifications will change the chromatin configuration without changing the DNA sequence. Somatic cells can be exposed to small molecules that may be able to reduce the chances of having incomplete chromatin modification. Two epigenetic modifying factors are a DNA methyltranferase inhibitor, zebularine (Zeb), and a histone deacetylase inhibitor, valproic acid (VPA). By inducing gene expression with the epigenetic modifiers, the cells may be stimulated to reprogram more efficiently than cells with lower gene expression. In the first experiment, three bovine ADS cell lines were treated with VPA or Zeb to observe the changes in expression levels of Oct4, Sox2, and Nanog (pluripotency-associated genes). The cells were treated for a period of 5, 7,10, or 14 days. VPA led to the highest increase of the pluripotency genes; however, both treatments may have produced a partial reprogramming. This partial reprogramming may result in the bovine ADS cells reaching complete pluripotency when combined with a reprogramming technique. In the second experiment, three bovine ADS cell lines were treated with VPA or Zeb for five days then followed with transduction using lentivirus. Oct4, Sox2, and Nanog were increased the highest when using epigenetic modifiers. Statistical differences for expression of the pluripotency-associated genes were found for cells treated with zebularine. While it was thought that viral transduction in combination with epigenetic modifiers would produce higher expression levels of the pluripotency-associated genes, this was not found to be true in this experiment.
Subjects/Keywords: bovine adult stem cells; induced pluripotent stem cells; stem cells
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APA (6th Edition):
Addison, M. K. (2012). Lentiviral transduction of epigenetically modified bovine adult stem cells. (Masters Thesis). Louisiana State University. Retrieved from etd-07162012-103728 ; https://digitalcommons.lsu.edu/gradschool_theses/4024
Chicago Manual of Style (16th Edition):
Addison, Meredith Kathleen. “Lentiviral transduction of epigenetically modified bovine adult stem cells.” 2012. Masters Thesis, Louisiana State University. Accessed March 07, 2021.
etd-07162012-103728 ; https://digitalcommons.lsu.edu/gradschool_theses/4024.
MLA Handbook (7th Edition):
Addison, Meredith Kathleen. “Lentiviral transduction of epigenetically modified bovine adult stem cells.” 2012. Web. 07 Mar 2021.
Vancouver:
Addison MK. Lentiviral transduction of epigenetically modified bovine adult stem cells. [Internet] [Masters thesis]. Louisiana State University; 2012. [cited 2021 Mar 07].
Available from: etd-07162012-103728 ; https://digitalcommons.lsu.edu/gradschool_theses/4024.
Council of Science Editors:
Addison MK. Lentiviral transduction of epigenetically modified bovine adult stem cells. [Masters Thesis]. Louisiana State University; 2012. Available from: etd-07162012-103728 ; https://digitalcommons.lsu.edu/gradschool_theses/4024
UCLA
4.
Megerdichian, Silva.
Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects.
Degree: Oral Biology, 2013, UCLA
URL: http://www.escholarship.org/uc/item/4zz5k216
► Adipose tissue has attracted great interest as an alternative stem cell source with the same multipotent properties as mesenchymal stem cells (MSCs). However, the stromal…
(more)
▼ Adipose tissue has attracted great interest as an alternative stem cell source with the same multipotent properties as mesenchymal stem cells (MSCs). However, the stromal vascular fraction (SVF) of adipose tissue contains a heterogeneous population of cells, which hamper its regenerative ability. We previously purified human adipose-derived Perivascular Stem Cells (PSCs) from SVF and showed that PSCs were capable of making significantly more bone compared to the SVF when implanted in the mouse muscle. Objectives: To evaluate the effectiveness of PSCs in the healing of mouse critical-size calvarial defects. Methods: Critical size (3mm) defects were created in the parietal bone of 50 adult SCID mice. Defects were either treated with an apatite coated PLGA scaffold alone, scaffold with human SVF or scaffold with human PSCs. Healing was monitored by live MicroCT scans at 0,2,4 and 6 weeks post injury. At 8 weeks postoperative, subjects were sacrificed and high-resolution microCT scanning was performed to observe total bone formation followed by histological analysis. Immunohistochemistry was performed to study expression of key osteogenic markers such as Osteopontin (OPN), Osteocalcin (OCN), Bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Results: PSCs resulted in a significantly more healing of the defect sites (69%) as opposed to 25% healing in the SVF models at 6 weeks. H&E staining revealed that the PSC group showed more and higher quality new bone in comparison with the SVF samples. Immunohistochemical staining of the defect sites showed that PSCs induced significant increases in osteogenic growth factor elaboration (BMP2, VEGF), significant evidence of OPN+, OCN+ osteogenesis, and ultimately significant calvarial defect re-ossification. Conclusion: Our results indicate that adipose-derived PSCs are a new cell source for future efforts in skeletal regenerative medicine. Further research to investigate PSCs induced healing in larger animals is needed to further unfold the haling potential of PSCs and understand its mechanism of action.
Subjects/Keywords: Dentistry; Biomedical engineering; Adipose Tissue; Adult Stem Cells; Mesenchymal stem cells; Perivascular Stem Cells
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APA (6th Edition):
Megerdichian, S. (2013). Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/4zz5k216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Megerdichian, Silva. “Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects.” 2013. Thesis, UCLA. Accessed March 07, 2021.
http://www.escholarship.org/uc/item/4zz5k216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Megerdichian, Silva. “Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects.” 2013. Web. 07 Mar 2021.
Vancouver:
Megerdichian S. Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects. [Internet] [Thesis]. UCLA; 2013. [cited 2021 Mar 07].
Available from: http://www.escholarship.org/uc/item/4zz5k216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Megerdichian S. Adipose-Derived Perivascular Stem Cells Heal Critical Size Mouse Calvarial Defects. [Thesis]. UCLA; 2013. Available from: http://www.escholarship.org/uc/item/4zz5k216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Cambridge
5.
Andersson Rolf, Amanda.
Application and Development of Advanced Genetic Tools to Study Adult Stem Cells.
Degree: PhD, 2018, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/275464
► Abstract Thesis Title: Application and Development of Advanced Genetic Tools to Study Adult Stem Cells By: Amanda Andersson Rolf In adult mammals, the gastrointestinal (GI)…
(more)
▼ Abstract
Thesis Title: Application and Development of Advanced Genetic Tools to Study Adult Stem Cells
By: Amanda Andersson Rolf
In adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate among the endodermal tissues. The harsh luminal environment of the GI tract necessitates replenishment of epithelial cells to maintain organ structure and function during routine turnover and injury repair. This delicate balance between gain and loss of cells is called tissue homeostasis, and multipotent tissue specific adult stem cells serve as the continuous source of self-renewal. Due to their important contribution to homeostatic maintenance the proliferative capacity of the stem cells needs to be tightly controlled, as an imbalance can result in diverse pathologies such as cancer or insufficient injury repair. Despite the crucial role for regulatory processes the molecular mechanisms and the genes governing these processes remain poorly understood.
Rnf43 and its paralogue Znrf3 (RZ) act as tumour suppressors in the intestine, but their role in the gastric epithelium has not been previously investigated. Using a novel unpublished stomach specific CreERT2 expressing mouse line I found that simultaneous knockout of RZ (RZ DKO) result in gastric hyperplasia of the corpus epithelium. Gastric RZ DKO organoids show independence from the essential growth factor Rspondin-1 but require exogenous Wnt. A similar exogenous Wnt dependence was identified in a human gastric cancer cell line harbouring homozygous Rnf43 inactivating mutations. Thus, Wnt secretion inhibition might provide a new treatment paradigm for a subset of patients carrying Rnf43 mutations.
The prominent role of the E3s Rnf43 and Znrf3 in the intestinal and gastric epithelial led to the question of whether other E3s either closely related to RZ or specifically expressed in stem or niche cells could play a role in homeostatic regulation, specifically in the small intestine. Using a retroviral overexpression screen I identified Rnf24 and Rnf122, two E3s that rendered intestinal organoids insensitive to withdrawal of the BMP inhibitor Noggin. Moreover, potential substrate candidates located at the cell surface membrane were identified and the generation of in vivo models initiated to provide a basis for further studies investigating the role of these E3s. In trying to address the function of the abovementioned genes using in vitro functional genetics I identified gaps in the current technology for organoid genetic engineering. I therefore developed two gene editing methods; a gRNA concatemer system allowing simultaneous knockout of multiple genes and CRISPR-FLIP enabling generation of conditional gene knockouts
In summary, this thesis describes the first stomach specific knockout of Rnf43 and Znrf3 in the gastric epithelium, showing that it results in gastric hyperplasia located to the corpus epithelium. The dependence of the Rnf43 and Znrf3 knockout epithelium on exogenous Wnt signalling provides a potential treatment strategy for a subset of…
Subjects/Keywords: CRISPR; organoids; adult stem cells; gastrointestinal tract
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APA (6th Edition):
Andersson Rolf, A. (2018). Application and Development of Advanced Genetic Tools to Study Adult Stem Cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/275464
Chicago Manual of Style (16th Edition):
Andersson Rolf, Amanda. “Application and Development of Advanced Genetic Tools to Study Adult Stem Cells.” 2018. Doctoral Dissertation, University of Cambridge. Accessed March 07, 2021.
https://www.repository.cam.ac.uk/handle/1810/275464.
MLA Handbook (7th Edition):
Andersson Rolf, Amanda. “Application and Development of Advanced Genetic Tools to Study Adult Stem Cells.” 2018. Web. 07 Mar 2021.
Vancouver:
Andersson Rolf A. Application and Development of Advanced Genetic Tools to Study Adult Stem Cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2018. [cited 2021 Mar 07].
Available from: https://www.repository.cam.ac.uk/handle/1810/275464.
Council of Science Editors:
Andersson Rolf A. Application and Development of Advanced Genetic Tools to Study Adult Stem Cells. [Doctoral Dissertation]. University of Cambridge; 2018. Available from: https://www.repository.cam.ac.uk/handle/1810/275464
Columbia University
6.
Melamed, David Eric.
Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry.
Degree: 2018, Columbia University
URL: https://doi.org/10.7916/D8XK9Z1Q
► Adult stem cells are vital to animal biology, tasked with replenishing cells in a variety of tissue types. Historically, there have been two contrasting models…
(more)
▼ Adult stem cells are vital to animal biology, tasked with replenishing cells in a variety of tissue types. Historically, there have been two contrasting models of stem cell behavior, “single-cell asymmetry,” where each stem cell is generally long lived and is responsible for perpetual daughter (non-stem) cell production, and “population asymmetry,” where a group of stem cells maintain population numbers while producing non-stem cell daughters, but individual stem cells undergo stochastic competition leading to frequent loss or amplification of individual lineages. Our work examines Drosophila ovarian Follicle Stem Cells (FSCs), which are somatic adult stem cells organized as a population of 14-16 cells within each germarium. FSCs are responsible for the production of two distinct somatic daughter cell types at opposite borders of the stem cell population. The FSCs are arranged in three anteroposterior layers; posterior “layer 1” FSCs divide faster and directly produce Follicle Cells (FCs), while anterior “layer 2 and 3” FSCs divide more slowly and give rise to Escort Cells (ECs). We have examined how signaling pathways contribute individually to FSC behavior, using clonal analysis to manipulate individual FSC genotypes and subsequently determine how autonomous FSC properties and competition among FSCs is affected. Our data indicate that Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) and Wnt pathways are primarily responsible for regulating location, proliferation and differentiation in FSCs. The activities of Hedgehog (Hh), Hippo (Hpo), and Phosphoinositide 3-kinase (PI3K) pathways are also shown to be important for FSC competition.
Subjects/Keywords: Biology; Cellular signal transduction; Adult stem cells
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APA (6th Edition):
Melamed, D. E. (2018). Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8XK9Z1Q
Chicago Manual of Style (16th Edition):
Melamed, David Eric. “Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry.” 2018. Doctoral Dissertation, Columbia University. Accessed March 07, 2021.
https://doi.org/10.7916/D8XK9Z1Q.
MLA Handbook (7th Edition):
Melamed, David Eric. “Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry.” 2018. Web. 07 Mar 2021.
Vancouver:
Melamed DE. Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Mar 07].
Available from: https://doi.org/10.7916/D8XK9Z1Q.
Council of Science Editors:
Melamed DE. Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8XK9Z1Q
University of Toronto
7.
Xu, Wenjun.
Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship.
Degree: PhD, 2017, University of Toronto
URL: http://hdl.handle.net/1807/80709
► Adult neural stem cells (NSC) reside in the periventricular region along the entire neuaxis. It is thought that a subset of mature astrocytes, expressing glial…
(more)
▼ Adult neural
stem cells (NSC) reside in the periventricular region along the entire neuaxis. It is thought that a subset of mature astrocytes, expressing glial fibrillary acidic protein (GFAP), known as definitive NSCs (dNSC) are responsible for neurogenesis within the
adult forebrain. We have identified a novel population of a rare, primitive NSC (pNSC) expressing low level of the pluripotency marker, Oct4. Both dNSC and pNSC can be isolated in vitro using neurosphere assays and differentiate into glial and neuronal cell types. Transplantation studies of pure pNSCs into the anterior rostral migratory stream of mice produced migrating neuroblasts and neurons in the olfactory bulb suggesting a potential lineage relationship between pNSCs and downstream progenitor
cells. Using transgenic mouse models whereby dNSCs are labeled using a Cre-Lox system then subsequently ablated using the thymidine kinase system under the GFAP promoter, we have shown that pNSCs are non-GFAP expressing and can give rise to dNSCs in the forebrain. By taking advantage of the unique marker expression of Oct4 in pNSCs, we used Oct4CreERT2;ROSAyfpfl/fl;GFAPtk mice to selectively label pNSCs followed by complete depletion of dNSCs. As predicted, some dNSCs that returned over time expressed YFP, revealing a direct contribution from pre-labeled Oct4 expressing pNSCs. Together, these findings confirm the NSC lineage relationship in vivo, whereby the dNSC lies downstream of the pNSC in the
adult forebrain.
In the non-neurogenic spinal cord niche, we have isolated pNSC and dNSC populations throughout development. We suggest a similar lineage relationship based on in vitro passaging experiments. Interestingly, the most abundant protein within mature myelin, myelin basic protein (MBP), inhibits proliferation which terminates NSC derived sphere formation in vitro. In a transgenic mouse model with conditional knock-out of MBP, the shiverer-/- mouse, there is a significant enhancement of the number of NSCs isolated both naively and following injury compared to littermate or non-injured controls respectively.
In conclusion, we have identified two distinct NSC populations within the
adult central nervous system that can be activated following injury but suppressed by MBP. Understanding the factors and conditions that impact these distinct populations of
cells will shed light into developing novel
stem cell-based regenerative medicine strategies.
Advisors/Committee Members: Morshead, Cindi M, Medical Science.
Subjects/Keywords: Adult; Adult Stem Cells; Myelin; Neural Stem Cells; Regenerative Medicine; Spinal Cord Injury; 0317
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APA (6th Edition):
Xu, W. (2017). Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/80709
Chicago Manual of Style (16th Edition):
Xu, Wenjun. “Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship.” 2017. Doctoral Dissertation, University of Toronto. Accessed March 07, 2021.
http://hdl.handle.net/1807/80709.
MLA Handbook (7th Edition):
Xu, Wenjun. “Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship.” 2017. Web. 07 Mar 2021.
Vancouver:
Xu W. Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1807/80709.
Council of Science Editors:
Xu W. Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and lineage Relationship. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/80709
Hong Kong University of Science and Technology
8.
Yi, Ran LIFS.
Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter.
Degree: 2016, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-100405
;
https://doi.org/10.14711/thesis-b1626980
;
http://repository.ust.hk/ir/bitstream/1783.1-100405/1/th_redirect.html
► Somatic stem cells, or adult stem cells, have the ability to replenish tissues throughout the body. Adult stem cells are able to self-renew and differentiate.…
(more)
▼ Somatic stem cells, or adult stem cells, have the ability to replenish tissues throughout the body. Adult stem cells are able to self-renew and differentiate. In particular, stem cells play important roles in tissue maintenance and regeneration. However, the regenerative capacity of somatic stem cells declines dramatically in some diseases and ageing. Recent finding suggests the notion that stem cells spontaneously proliferate and subsequently are depleted in old tissues. As somatic stem cell is only a small percentage of total cell number within the tissue and heterogeneity exists within this population, it is a hurdle to identify and isolate these cell populations from adult tissues. Traditionally, identification of low turnover somatic stem cells relies on the label retention technique. However, detection of DNA labels requires cell fixation and the purity of somatic stem cells is questionable. Even though fluorescence activated cell sorting (FACS) is a powerful method to separate them from a heterogeneous mixture of biological cells in vitro, it requires known markers and available antibodies for specific stem cell populations. To lineage trace a specific somatic stem cell population in vivo, inducible recombinases and multicolor fluorescent reporters have been extensively used. In this study, we aim to generate a transgenic mouse line that can serve as both a lineage tracer and a cell division counter up to two rounds of cell cycle. Lineage tracing of specific cells along with cell cycle history of the low turnover somatic stem cells will provide a better understanding of how they behave during homeostasis, pathological conditions and ageing.
Subjects/Keywords: Adult stem cells
; Muscle cells
; Musculoskeletal system
; Cell cycle
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APA (6th Edition):
Yi, R. L. (2016). Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-100405 ; https://doi.org/10.14711/thesis-b1626980 ; http://repository.ust.hk/ir/bitstream/1783.1-100405/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yi, Ran LIFS. “Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter.” 2016. Thesis, Hong Kong University of Science and Technology. Accessed March 07, 2021.
http://repository.ust.hk/ir/Record/1783.1-100405 ; https://doi.org/10.14711/thesis-b1626980 ; http://repository.ust.hk/ir/bitstream/1783.1-100405/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yi, Ran LIFS. “Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter.” 2016. Web. 07 Mar 2021.
Vancouver:
Yi RL. Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2016. [cited 2021 Mar 07].
Available from: http://repository.ust.hk/ir/Record/1783.1-100405 ; https://doi.org/10.14711/thesis-b1626980 ; http://repository.ust.hk/ir/bitstream/1783.1-100405/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yi RL. Tracking low turnover somatic stem and progenitor cells in vivo using a lineage-specific cell cycle counter. [Thesis]. Hong Kong University of Science and Technology; 2016. Available from: http://repository.ust.hk/ir/Record/1783.1-100405 ; https://doi.org/10.14711/thesis-b1626980 ; http://repository.ust.hk/ir/bitstream/1783.1-100405/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
9.
Jiang, Yindi.
Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis.
Degree: 2014, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/3947
► The maintenance of the resident adult neural stem/progenitor cell (NSPC) pool depends on the precise balance of proliferation, differentiation, and maintenance of the undifferentiated state.…
(more)
▼ The maintenance of the resident
adult neural
stem/progenitor cell (NSPC) pool depends on the precise balance of proliferation, differentiation, and maintenance of the undifferentiated state. Identifying the mechanisms that regulate this balance in
adult hippocampal NSPCs can provide insight into basic neurogenesis principles important for tissue homeostasis and preventing tumor formation. Pharmacological inhibition of histone deacetylases (HDACs), a class of histone-modifying enzymes, have promising effects in cancer
cells, yet the specific roles of individual HDACs in
adult NSPCs are unclear. In this dissertation, I focus on dissecting the roles of two different HDACs in
adult hippocampal neurogenesis: the Class I HDAC, HDAC3 and the Class IIa HDAC, HDAC5 as well as the Class IIa HDAC binding partner, myocyte enhancer factor 2 (MEF2).
Using conditional knockout (cKO) mice and in vitro cell culture, I show that histone deacetylase 3 (HDAC3) is required for the proliferation of
adult NSPCs. Detailed cell cycle analysis of NSPCs from Hdac3 cKO mice reveals a defect in cell cycle progression through G2/M phase, but not S phase. Moreover, HDAC3 controls G2/M phase progression mainly through post-translational stabilization of the G2/M cyclin- dependent kinase-1 (CDK1). These results demonstrate that HDAC3 plays a critical role in NSPC proliferation.
HDAC5 is the most abundant Class IIa HDAC in
adult dentate gyrus. HDAC5 is only expressed in immature and mature neurons. Using Hdac5 knockout mice and in vitro cell culture, I show that HDAC5 is necessary and sufficient to restrict the neuronal differentiation of NSPCs. However, the detailed mechanisms are yet to be determined.
Class IIa HDACs bind to myocyte enhancer factor 2 (MEF2) in the nucleus to repress transcription of pro-neuronal genes. Thus, we also examined the function of Mef2 genes in
adult hippocampal neurogenesis. In
adult hippocampus, the three most highly expressed MEF2 proteins are MEF2A, 2C, and 2D, which are expressed in immature and mature neurons similar to HDAC5. We have shown that one synthetic small molecule, Isoxazole-9 (Isx-9) could trigger neuronal differentiation robustly in vitro and in vivo. Inducible knockout of all three Mef2 genes specifically in NSPCs and their progeny revealed their critical roles in mediating Isx-9 induced neurogenesis and baseline neurogenesis.
In summary, these results demonstrate that HDACs and MEF2 control different stages of
adult hippocampal neurogenesis and suggest that strategies aimed at pharmacological modulation of these proteins may be beneficial for tissue regeneration and controlling tumor cell growth in mammalian brain.
Advisors/Committee Members: Zhang, Chun-Li, Olson, Eric N., Johnson, Jane E., Hsieh, Jenny.
Subjects/Keywords: Adult Stem Cells; CDC2 Protein Kinase; G2 Phase; Histone Deacetylases; Mitosis; Neural Stem Cells
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APA (6th Edition):
Jiang, Y. (2014). Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/3947
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jiang, Yindi. “Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021.
http://hdl.handle.net/2152.5/3947.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jiang, Yindi. “Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis.” 2014. Web. 07 Mar 2021.
Vancouver:
Jiang Y. Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2152.5/3947.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jiang Y. Roles of HDACs and MEF2 in Adult Hippocampal Neurogenesis. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/3947
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Miami
10.
Carballosa, Carlos M.
The Effects of Nicotine on Mesenchymal Stem Cell Function.
Degree: MS, Biomedical Engineering (Engineering), 2012, University of Miami
URL: https://scholarlyrepository.miami.edu/oa_theses/356
► This research focuses on the effects nicotine exposure has on Human, Bone Marrow Derived Mesenchymal Stem Cell (MSC) proliferation, migration and differentiation potential. Nicotine,…
(more)
▼ This research focuses on the effects nicotine exposure has on Human, Bone Marrow Derived Mesenchymal
Stem Cell (MSC) proliferation, migration and differentiation potential. Nicotine, the quintessential compound responsible for a smoker’s addiction to cigarettes, is an organic compound, whose effects are either positive or negative depending on the dose of nicotine metabolized. In low concentrations, nicotine has been shown to induce angiogenesis and improve diseases such as Alzheimer’s and Parkinson’s. In high doses, however, nicotine has been shown to have detrimental effects including hindering both embryonic
stem cell development and skeletal healing. Although much has been discovered about the effects of nicotine at the cellular level, information on its effect on MSC function are not fully understood. In order to evaluate such effects, four independent studies were conducted to evaluate the proliferation, migration and differentiation potential of MSC exposed to nicotine levels similar to those seen in the saliva of chronic smokers. Results from all studies clearly showed nicotine had an adverse effect on inherent MSC characteristics. MSCs exposed to nicotine containing media experienced a significant reduction in proliferation rate, overall distance traveled, average cell speed and gene expression of various osteogenic and migratory markers. Although the presence of nicotine alone has shown to adversely effect the proliferation, migration and osteogenic potential of MSC, additional studies must be conducted to see how these results will change in the presence of the remaining cigarette smoke compounds.
Advisors/Committee Members: Herman S. Cheung, Chun-Yuh C. Huang, Guy A. Howard.
Subjects/Keywords: Mesenchymal Stem Cells; Nicotine; Smoking; Differentiation Potential; Adult Stem Cells; Bone Marrow
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APA (6th Edition):
Carballosa, C. M. (2012). The Effects of Nicotine on Mesenchymal Stem Cell Function. (Thesis). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_theses/356
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Carballosa, Carlos M. “The Effects of Nicotine on Mesenchymal Stem Cell Function.” 2012. Thesis, University of Miami. Accessed March 07, 2021.
https://scholarlyrepository.miami.edu/oa_theses/356.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Carballosa, Carlos M. “The Effects of Nicotine on Mesenchymal Stem Cell Function.” 2012. Web. 07 Mar 2021.
Vancouver:
Carballosa CM. The Effects of Nicotine on Mesenchymal Stem Cell Function. [Internet] [Thesis]. University of Miami; 2012. [cited 2021 Mar 07].
Available from: https://scholarlyrepository.miami.edu/oa_theses/356.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Carballosa CM. The Effects of Nicotine on Mesenchymal Stem Cell Function. [Thesis]. University of Miami; 2012. Available from: https://scholarlyrepository.miami.edu/oa_theses/356
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of South Carolina
11.
Harris, Greg M.
Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification.
Degree: PhD, Chemical Engineering, 2013, University of South Carolina
URL: https://scholarcommons.sc.edu/etd/2557
► Tissue engineering is a broad field geared toward improving or replacing biological material and comprises an immense collection of biological nuances to consider before…
(more)
▼ Tissue engineering is a broad field geared toward improving or replacing biological material and comprises an immense collection of biological nuances to consider before strategies for clinical applications can be fully realized. Physical and biochemical signals are responsible for making up a cell's microenvironment to guide morphology and function through cell-extracellular matrix signaling, cell-cell signaling, and soluble signaling. In particular, a deeper understanding of these cell-extra cellular matrix factors guiding
stem cell adhesion, spreading, and differentiation is crucial to harnessing the potential to develop tissue for regenerative purposes. Mounting evidence suggests that physical cues are a key to understanding the potential of
stem cells and significant efforts have been made to begin to parse the effects of cell-matrix interactions, yet little is known about the interplay in guiding cell signaling. The work presented here focuses on utilizing novel methods and materials to deconstruct individual cell-matrix interactions and gain a deeper understanding of the cooperative signaling behaviors for mesenchymal and embryonic
stem cells.
Micropatterning studies utilizing dip pen nanolithography showed that physical signals in the microenvironment are vital to regulating mesenchymal
stem cell adhesion. Matrix elasticity, ligand density, and adhesion topography were individually altered to observe single cell adhesion and spreading with matrix elasticity proving to regulate the adhesion and spreading of the
cells. Photolithography based studies detailing cell spreading and matrix elasticity showed that when confining single
cells into different geometric shapes and sizes on a matrix of tunable elasticity, cell shape and size ultimately became responsible for
stem cell lineage commitment over matrix elasticity. Signaling pathway inhibition experiments utilizing nocodazole and Y-27632 suggested that RhoA is a key regulator of cell response to the cooperative effect of these tunable substrate variables. Embryonic
stem cells were then micropatterned on novel UV/ozone modified polystyrene to detail and observe the physical effects on single embryonic
stem cells. Micropatterned
cells were able to be cultured for up to 48 hours on patterns while forming stress fibers and focal adhesions similar to somatic
cells, thereby demonstrating their responsiveness to extracellular matrix cues while maintaining expression of pluripotency transcription factor Oct4. The results from this work validate the immense importance of physical signaling and the effects on mesenchymal and embryonic
stem cells. By understanding the effects of physical signaling in conjunction with biochemical signaling in controlling cell spreading and lineage commitment, tissue engineering is able to draw one step closer to potential applications for repairing and replacing biological function.
Advisors/Committee Members: Ehsan Jabbarzadeh.
Subjects/Keywords: Chemical Engineering; Engineering; Adult Stem Cells; Biomaterials; Differentiation; Embryonic Stem Cells; Induced Pluripotent Stem Cells; Micropatterning
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Harris, G. M. (2013). Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification. (Doctoral Dissertation). University of South Carolina. Retrieved from https://scholarcommons.sc.edu/etd/2557
Chicago Manual of Style (16th Edition):
Harris, Greg M. “Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification.” 2013. Doctoral Dissertation, University of South Carolina. Accessed March 07, 2021.
https://scholarcommons.sc.edu/etd/2557.
MLA Handbook (7th Edition):
Harris, Greg M. “Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification.” 2013. Web. 07 Mar 2021.
Vancouver:
Harris GM. Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification. [Internet] [Doctoral dissertation]. University of South Carolina; 2013. [cited 2021 Mar 07].
Available from: https://scholarcommons.sc.edu/etd/2557.
Council of Science Editors:
Harris GM. Parsing the Effects of Physical Microenvironmental Cues on Stem Cell Adhesion and Lineage Specification. [Doctoral Dissertation]. University of South Carolina; 2013. Available from: https://scholarcommons.sc.edu/etd/2557
University of Iowa
12.
Lynch, Thomas John.
Adult stem cells in the trachea and tracheal submucosal glands.
Degree: PhD, Anatomy and Cell Biology, 2016, University of Iowa
URL: https://ir.uiowa.edu/etd/6464
► Breathing is essential for human life, yet tens of millions of people in the U.S. alone suffer from lung diseases. With each breath, lungs…
(more)
▼ Breathing is essential for human life, yet tens of millions of people in the U.S. alone suffer from lung diseases. With each breath, lungs are exposed to the external environment. Inhaled air first passes through the trachea, bronchi, and finally the bronchioles before it reaches the alveoli where gases are exchanged. A barrier of epithelial
cells protects the airways. In addition, epithelial glands also secrete protein-rich fluids onto the airway surfaces to help maintain sterility. Injury, disease, or other factors can damage these
cells, and regiospecific
stem cells (SCs) can divide to replace them. However, many important details about lung SCs are still unknown. For example, what processes control SC division? How do region-specific SCs differ from one another? And how does disease or injury impact SC biology? We found that some processes that regulate lung development also control
adult SC division following injury. We show that SCs from airway glands give rise to surface epithelial cell types and glandular cell types. In contrast, surface SCs only generated surface cell types. Finally, we identify a type of cell in the glands that can regenerate surface cell types after severe injury. These studies provide new insights into the neighborhoods in which SCs reside in the large airways and processes that control their contribution to airway repair following injury. Overall, this research provides important new insights into
adult SC biology and conditions affecting lung health.
Advisors/Committee Members: Engelhardt, John F. (supervisor).
Subjects/Keywords: Adult stem cells; Developmental biology; Facultative stem cell; Multipotential differentiation; Stem cell microenvironment interactions; Stem cell niche; Cell Anatomy; Cell Biology
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APA (6th Edition):
Lynch, T. J. (2016). Adult stem cells in the trachea and tracheal submucosal glands. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/6464
Chicago Manual of Style (16th Edition):
Lynch, Thomas John. “Adult stem cells in the trachea and tracheal submucosal glands.” 2016. Doctoral Dissertation, University of Iowa. Accessed March 07, 2021.
https://ir.uiowa.edu/etd/6464.
MLA Handbook (7th Edition):
Lynch, Thomas John. “Adult stem cells in the trachea and tracheal submucosal glands.” 2016. Web. 07 Mar 2021.
Vancouver:
Lynch TJ. Adult stem cells in the trachea and tracheal submucosal glands. [Internet] [Doctoral dissertation]. University of Iowa; 2016. [cited 2021 Mar 07].
Available from: https://ir.uiowa.edu/etd/6464.
Council of Science Editors:
Lynch TJ. Adult stem cells in the trachea and tracheal submucosal glands. [Doctoral Dissertation]. University of Iowa; 2016. Available from: https://ir.uiowa.edu/etd/6464
Tampere University
13.
Zhou, Mia.
Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells.
Degree: 2018, Tampere University
URL: https://trepo.tuni.fi/handle/10024/102859
► The amniotic membrane (AM) has many desirable qualities for tissue engineering. The three main objectives of this study were to investigate 1) adipose-derived stem cell…
(more)
▼ The amniotic membrane (AM) has many desirable qualities for tissue engineering. The three main objectives of this study were to investigate 1) adipose-derived stem cell (ASC) cultivation and possible differentiation on AM, 2) co-cultivation of ASCs and human umbilical vein endothelial cells (HUVECs) on AM for enhanced angiogenesis, 3) effects of cell cultivation on the mechanical properties of AM. Denuded AM was cut and placed to cover the bottom of 6-well multidishes, 1/3 of AM-covered wells were seeded with only ASCs, 1/3 with only HUVECs and 1/3 with both. Half were cultured with adipose medium (ADM) and half with endothelial medium for three weeks (EM). After three weeks, the cultivated AMs were analyzed with quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence photography, hematoxylin-eosin staining and microtomography. Tensile strength tests were conducted with separate AM samples cultivated in special scaffolds along
with nitrocellulose paper. Results showed no visible adipose formation, nor clear angiogenic tube formation. Engineering stress endured by AM during tension testing decreased as cultivation time lengthened. ASCs showed great viability on AM. HUVECs showed viability in EM based on von Willebrand factor expression. HUVEC proliferation was not seen in ADM. In conclusion, AM is a suitable scaffold for ASCs, better induction agents for adipocyte differentiation and tube formation should be explored, and a better method to detect HUVECs from the co-cultivation wells is needed.
Subjects/Keywords: tissue engineering; amniotic membrane; adult stem cells; adipose-derived stem cells; human umbilical vein endothelial cells; angiogenesis
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APA ·
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Manager
APA (6th Edition):
Zhou, M. (2018). Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells. (Masters Thesis). Tampere University. Retrieved from https://trepo.tuni.fi/handle/10024/102859
Chicago Manual of Style (16th Edition):
Zhou, Mia. “Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells.” 2018. Masters Thesis, Tampere University. Accessed March 07, 2021.
https://trepo.tuni.fi/handle/10024/102859.
MLA Handbook (7th Edition):
Zhou, Mia. “Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells.” 2018. Web. 07 Mar 2021.
Vancouver:
Zhou M. Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells. [Internet] [Masters thesis]. Tampere University; 2018. [cited 2021 Mar 07].
Available from: https://trepo.tuni.fi/handle/10024/102859.
Council of Science Editors:
Zhou M. Amniotic membrane as a scaffold for human adipose stem cells and umbilical vein endothelial cells. [Masters Thesis]. Tampere University; 2018. Available from: https://trepo.tuni.fi/handle/10024/102859
University of Michigan
14.
Tsan, Yao-Chang.
Role of a Novel microRNA in Adult Neurogenesis.
Degree: PhD, Cell and Developmental Biology, 2014, University of Michigan
URL: http://hdl.handle.net/2027.42/107309
► Multipotent, self-renewing stem cells which are present throughout the developing nervous system remain in discrete regions of the adult brain. In the subventricular zone (SVZ)…
(more)
▼ Multipotent, self-renewing
stem cells which are present throughout the developing nervous system remain in discrete regions of the
adult brain. In the subventricular zone (SVZ) signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, Noggin appear to play a critical role in controlling neural
stem cell (NSC) behavior. To examine the function of this signaling pathway in the intact nervous system, we have developed a transgenic mouse model in which Noggin expression can be induced specifically in NSC via a Nestin promoter-driven reverse tetracycline-controlled transactivator (rtTA). In
adult animals, induction of Noggin expression promotes proliferation of NSC in the SVZ, and shifts the differentiation of NSC from mature astrocytes to transit amplifying
cells and oligodendrocyte precursor
cells without depleting the NSC population.
Interestingly, over-expression of Noggin in the
adult SVZ neural
stem cells also inhibits the expression of a novel microRNA-410 (miR-410). miR-410 is expressed in the developing nervous system, remaining in the germinal zones of the
adult brain. Over-expression of miR-410 in SVZ derived neurospheres consistently inhibited neuronal and oligodendrocyte differentiation while promoting the formation of astrocytes. Conversely, inhibition of miR-410 activity in NSC promoted neuronal and decreased astroglial differentiation. In addition, over-expression of miR-410 rescued the increase in neuronal differentiation and the decrease in astroglial differentiation caused by Noggin over-expression. Using computer prediction algorithms and luciferase reporter assays, we identified multiple neurogenic genes including Elavl4 as one of the downstream targets of miR-410 via the canonical miRNA-3’UTR interaction. Over-expression of Elavl4 transcripts without the endogenous 3’ UTR rescued the decrease in neuronal differentiation caused by miR-410 over-expression. Interestingly, we also observed that miR-410 affected neurite morphology. Over-expression of miR-410 resulted in the formation of short, unbranched neurites. These results demonstrate that miR-410 controls the crucial lineage choice of
adult neural
stem cells between neurons and glial
cells by controlling the expression of neurogenic genes, and suggest a method to regulate NSC differentiation following disease, injury or aging.
Advisors/Committee Members: O'Shea, Sue (committee member), Parent, Jack M. (committee member), Giger, Roman (committee member), Goldman, Daniel J. (committee member).
Subjects/Keywords: MicroRNA; Adult Neural Stem Cells; Molecular, Cellular and Developmental Biology; Science
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Manager
APA (6th Edition):
Tsan, Y. (2014). Role of a Novel microRNA in Adult Neurogenesis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/107309
Chicago Manual of Style (16th Edition):
Tsan, Yao-Chang. “Role of a Novel microRNA in Adult Neurogenesis.” 2014. Doctoral Dissertation, University of Michigan. Accessed March 07, 2021.
http://hdl.handle.net/2027.42/107309.
MLA Handbook (7th Edition):
Tsan, Yao-Chang. “Role of a Novel microRNA in Adult Neurogenesis.” 2014. Web. 07 Mar 2021.
Vancouver:
Tsan Y. Role of a Novel microRNA in Adult Neurogenesis. [Internet] [Doctoral dissertation]. University of Michigan; 2014. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2027.42/107309.
Council of Science Editors:
Tsan Y. Role of a Novel microRNA in Adult Neurogenesis. [Doctoral Dissertation]. University of Michigan; 2014. Available from: http://hdl.handle.net/2027.42/107309
North Carolina State University
15.
Marvel, Skylar.
The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells.
Degree: MS, Biomedical Engineering, 2009, North Carolina State University
URL: http://www.lib.ncsu.edu/resolver/1840.16/2793
► Functional bone tissue engineering is a very important emerging interdisciplinary field of research. The treatments of bone loss, defects, trauma and disease often require replacement…
(more)
▼ Functional bone tissue engineering is a very important emerging interdisciplinary field of research. The treatments of bone loss, defects, trauma and disease often require replacement bone tissue or the use of bone substitutes. Functional bone tissue engineering attempts to create this needed replacement bone tissue using a patient’s
stem cells. One small aspect of this field involves being able to control the proliferation and osteogenic differentiation of a patient’s
stem cells with the eventual goal of creating an autologous bone graft in vitro to correct bone defects. Two possible types of
stem cells for this procedure are human bone marrow derived mesenchymal
stem cells (hMSCs) and human adipose derived
adult stem cells (hASCs), both of which have been shown to be capable of osteogenic differentiation. Many different stimuli are being actively researched to control this differentiation, such as fluid shear stress, tensile strain, electric fields, chemical signals and material properties of substrates to name a few. One newly investigated stimulus is low intensity pulsed ultrasound (LIPUS). Since the mid 1990s LIPUS has been used clinically to aid fracture healing and since 2000 has also been prescribed for the treatment of non-unions. Although the mechanisms have not been elucidated, LIPUS has been shown to increase expression of cellular osteogenic markers in vitro. However, the parameters of LIPUS have not been optimized for increasing osteogenic differentiation and the use of LIPUS has been untested on hASCs, both of which could potentially benefit the field of bone tissue engineering and are the focus of this body of work.
To explore the optimization of LIPUS parameters a custom ultrasound system was designed and built to give precise control over an extensive range of values for each stimulus parameter. There were several design criteria which included making the system automatable, insuring that the system can be used with standard incubators, and reducing the amount of laboratory space required to house the system. Once built, the ultrasound system was validated by testing three different pulse repetition frequency (PRF) parameter settings for inducing osteogenic differentiation of both hMSCs and hASCs. The first set of experiments investigated effects on hASCs and showed a significant increase in calcium accretion per cell with both 1 kHz and 100 Hz PRFs; however, this result was diminished by noting that the significant differences came from variations in amounts of DNA rather than increases in calcium. The effect caused by the presence of papain digest in experimental samples on the quantification of DNA was then studied and a change in the protocol for the DNA quantification assay was made. Using the modified assay a second set of experiments investigated the effects of LIPUS on hMSCs, and although the results were not significant, there was a trend of increased calcium accretion per cell with higher PRFs indicating that, of the three PRF settings tested, the 1 kHz PRF…
Advisors/Committee Members: Dr. Greg S. McCarty, Committee Member (advisor), Dr. Paul A. Dayton, Committee Co-Chair (advisor), Dr. Elizabeth G. Loboa, Committee Chair (advisor).
Subjects/Keywords: pulse repetition frequency; adipose derived adult stem cells
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APA (6th Edition):
Marvel, S. (2009). The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells. (Thesis). North Carolina State University. Retrieved from http://www.lib.ncsu.edu/resolver/1840.16/2793
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marvel, Skylar. “The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells.” 2009. Thesis, North Carolina State University. Accessed March 07, 2021.
http://www.lib.ncsu.edu/resolver/1840.16/2793.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marvel, Skylar. “The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells.” 2009. Web. 07 Mar 2021.
Vancouver:
Marvel S. The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells. [Internet] [Thesis]. North Carolina State University; 2009. [cited 2021 Mar 07].
Available from: http://www.lib.ncsu.edu/resolver/1840.16/2793.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marvel S. The Importance of Low Intensity Pulsed Ultrasound Parameters for Functional Bone Tissue Engineering using Adult Stem Cells. [Thesis]. North Carolina State University; 2009. Available from: http://www.lib.ncsu.edu/resolver/1840.16/2793
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Cambridge
16.
Rimland, Casey.
Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.
Degree: PhD, 2019, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/286011https://www.repository.cam.ac.uk/bitstream/1810/286011/2/Annex%20File%201%20EHBD%20Tissues%20DGE.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/3/Annex%20File%202%20EHBD%20Tissue%20Specific%20Genes.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/4/Annex%20File%203%20EHBD%20Tissue%20Gene%20Ontology%20Analyses.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/5/Annex%20File%204%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/6/Annex%20File%205%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue%20Gene%20Ontology%20Analyses.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/7/Annex%20File%206%20EHBD%20Tissue%20vs%20Organoids%20DGE.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/8/Annex%20File%207%20EHBD%20Tissues%20vs%20Organoids%20Gene%20Ontology.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/9/Annex%20File%208%20EHBD%20Organoids%20vs%20Organoids%20DGE.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/10/Annex%20File%209%20Genes%20Upregulated%20in%20both%20EHBD%20Organoids%20and%20Tissues.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/11/Annex%20File%2010%20Comparing%20EHBD%20Organoids%20to%20ISC%20Signature.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/12/Annex%20File%2011%20EHBD%20vs%20IHBD%20Organoids%20DGE.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/13/Annex%20File%2012%20IHBD_Huch%20vs%20EHBD%20Organoids%20Gene%20Ontology%20Analyses.xlsx
;
https://www.repository.cam.ac.uk/bitstream/1810/286011/14/Annex%20File%2013%20IHBD%20vs%20EHBD%20Tissues%20DGE.xlsx
► The biliary tree is a series of ductular tissues responsible for the drainage of bile produced by the liver and pancreatic secretions from the pancreas.…
(more)
▼ The biliary tree is a series of ductular tissues responsible for the drainage of bile produced by the liver and pancreatic secretions from the pancreas. The biliary tree is affected by a diversity of life- threatening diseases collectively called cholangiopathies. Cholangiopathies show regionalization, with some diseases such as biliary atresia predominantly targeting extrahepatic bile ducts (EHBDs) outside of the liver. Despite this, little is known on whether anatomical location within the biliary tree contributes to differences in functionality of biliary epithelium, especially in the EHBD compartment. Additionally, reports have demonstrated the possibility for in vitro culture of bile duct stem/progenitor cell organoids from both intrahepatic (IHBD) and EHBD sources. The relation of these organoid systems to each other, and to their tissue of origin, is largely unknown.
In this dissertation, I address these major questions by combining transcriptional analyses and in vitro culture of human bile duct organoids derived from primary IHBD and EHBD epithelium. First, I show that in vitro organoids can be derived from four regions of the human biliary tree: gallbladder, common bile duct, pancreatic duct, and intrahepatic bile ducts. Characterization of these organoids demonstrated expression of adult stem cell (LGR5/PROM1) and ductal (KRT19/KRT7) markers suggesting these cultures contained cells with a biliary stem/progenitor phenotype. Further, I show that IHBD organoids are distinct from EHBD organoids requiring different conditions for sustained growth. Using RNA-Sequencing, I demonstrate that primary tissues from different regions of the extrahepatic biliary tree display unique expression profiles and identify novel tissue-specific markers. I also show that only a limited number of these tissue specific differences are maintained in the in vitro organoids and that the organoids are very different from their tissue of origin. Finally, I demonstrate that IHBD, but not EHBD organoids, express a low-level of hepatocyte-specific markers under differentiation conditions.
Taken together, the work in this dissertation has uncovered regional specific markers for different anatomical regions of the human biliary tree. Further, I demonstrate that major differences exist between IHBD organoids and EHBD organoids in vitro and discover that only IHBD organoids have the capacity to express hepatocyte markers under differentiation conditions. Ultimately, these results may help to identify new targets for therapeutic development for cholangiopathies and regenerative medicine. They have also provided important insight to the understanding of both basic biliary physiology and also the field of biliary stem/progenitor cell organoids.
Subjects/Keywords: Biliary Tree; Extrahepatic Bile Duct; Organoids; Adult Stem Cells
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APA (6th Edition):
Rimland, C. (2019). Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/286011https://www.repository.cam.ac.uk/bitstream/1810/286011/2/Annex%20File%201%20EHBD%20Tissues%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/3/Annex%20File%202%20EHBD%20Tissue%20Specific%20Genes.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/4/Annex%20File%203%20EHBD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/5/Annex%20File%204%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/6/Annex%20File%205%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/7/Annex%20File%206%20EHBD%20Tissue%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/8/Annex%20File%207%20EHBD%20Tissues%20vs%20Organoids%20Gene%20Ontology.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/9/Annex%20File%208%20EHBD%20Organoids%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/10/Annex%20File%209%20Genes%20Upregulated%20in%20both%20EHBD%20Organoids%20and%20Tissues.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/11/Annex%20File%2010%20Comparing%20EHBD%20Organoids%20to%20ISC%20Signature.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/12/Annex%20File%2011%20EHBD%20vs%20IHBD%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/13/Annex%20File%2012%20IHBD_Huch%20vs%20EHBD%20Organoids%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/14/Annex%20File%2013%20IHBD%20vs%20EHBD%20Tissues%20DGE.xlsx
Chicago Manual of Style (16th Edition):
Rimland, Casey. “Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 07, 2021.
https://www.repository.cam.ac.uk/handle/1810/286011https://www.repository.cam.ac.uk/bitstream/1810/286011/2/Annex%20File%201%20EHBD%20Tissues%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/3/Annex%20File%202%20EHBD%20Tissue%20Specific%20Genes.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/4/Annex%20File%203%20EHBD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/5/Annex%20File%204%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/6/Annex%20File%205%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/7/Annex%20File%206%20EHBD%20Tissue%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/8/Annex%20File%207%20EHBD%20Tissues%20vs%20Organoids%20Gene%20Ontology.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/9/Annex%20File%208%20EHBD%20Organoids%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/10/Annex%20File%209%20Genes%20Upregulated%20in%20both%20EHBD%20Organoids%20and%20Tissues.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/11/Annex%20File%2010%20Comparing%20EHBD%20Organoids%20to%20ISC%20Signature.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/12/Annex%20File%2011%20EHBD%20vs%20IHBD%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/13/Annex%20File%2012%20IHBD_Huch%20vs%20EHBD%20Organoids%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/14/Annex%20File%2013%20IHBD%20vs%20EHBD%20Tissues%20DGE.xlsx.
MLA Handbook (7th Edition):
Rimland, Casey. “Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.” 2019. Web. 07 Mar 2021.
Vancouver:
Rimland C. Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 07].
Available from: https://www.repository.cam.ac.uk/handle/1810/286011https://www.repository.cam.ac.uk/bitstream/1810/286011/2/Annex%20File%201%20EHBD%20Tissues%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/3/Annex%20File%202%20EHBD%20Tissue%20Specific%20Genes.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/4/Annex%20File%203%20EHBD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/5/Annex%20File%204%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/6/Annex%20File%205%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/7/Annex%20File%206%20EHBD%20Tissue%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/8/Annex%20File%207%20EHBD%20Tissues%20vs%20Organoids%20Gene%20Ontology.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/9/Annex%20File%208%20EHBD%20Organoids%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/10/Annex%20File%209%20Genes%20Upregulated%20in%20both%20EHBD%20Organoids%20and%20Tissues.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/11/Annex%20File%2010%20Comparing%20EHBD%20Organoids%20to%20ISC%20Signature.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/12/Annex%20File%2011%20EHBD%20vs%20IHBD%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/13/Annex%20File%2012%20IHBD_Huch%20vs%20EHBD%20Organoids%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/14/Annex%20File%2013%20IHBD%20vs%20EHBD%20Tissues%20DGE.xlsx.
Council of Science Editors:
Rimland C. Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/286011https://www.repository.cam.ac.uk/bitstream/1810/286011/2/Annex%20File%201%20EHBD%20Tissues%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/3/Annex%20File%202%20EHBD%20Tissue%20Specific%20Genes.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/4/Annex%20File%203%20EHBD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/5/Annex%20File%204%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/6/Annex%20File%205%20Genes%20Upregulated%20in%20GBD%20and%20CBD%20vs%20PancD%20Tissue%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/7/Annex%20File%206%20EHBD%20Tissue%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/8/Annex%20File%207%20EHBD%20Tissues%20vs%20Organoids%20Gene%20Ontology.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/9/Annex%20File%208%20EHBD%20Organoids%20vs%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/10/Annex%20File%209%20Genes%20Upregulated%20in%20both%20EHBD%20Organoids%20and%20Tissues.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/11/Annex%20File%2010%20Comparing%20EHBD%20Organoids%20to%20ISC%20Signature.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/12/Annex%20File%2011%20EHBD%20vs%20IHBD%20Organoids%20DGE.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/13/Annex%20File%2012%20IHBD_Huch%20vs%20EHBD%20Organoids%20Gene%20Ontology%20Analyses.xlsx ; https://www.repository.cam.ac.uk/bitstream/1810/286011/14/Annex%20File%2013%20IHBD%20vs%20EHBD%20Tissues%20DGE.xlsx
University of Edinburgh
17.
Kilcoyne, Karen.
Early life programming of adult Leydig cell function.
Degree: PhD, 2014, University of Edinburgh
URL: http://hdl.handle.net/1842/9533
► There is increasing evidence to suggest that fetal events can predetermine reproductive health and general wellbeing in adulthood, a process termed 'fetal programming'. This refers…
(more)
▼ There is increasing evidence to suggest that fetal events can predetermine reproductive health and general wellbeing in adulthood, a process termed 'fetal programming'. This refers to the association between altered fetal growth/development and health disorders in adulthood e.g. the metabolic syndrome, which is linked to low male testosterone levels. Studies from both Europe and the USA have shown that adult male testosterone levels have been declining, independent of age. As low testosterone levels in aging men are associated with increased morbidity and mortality, this highlights the importance of investigating how testosterone levels are determined or potentially ‘programmed’ during fetal development. Evidence from human and rodent studies have shown that reduced fetal androgen exposure results in lower adult testosterone levels, although the mechanism(s) is unknown, to date. One way to explain how a fetal insult (e.g. androgen deficiency) could affect (testosterone producing) adult Leydig cells in adulthood, is if their progenitor cells were present during fetal life and were thus affected by such an insult. This hypothesis has been unexplored to date, due to the lack of a unifying/defining marker for adult Leydig progenitor cells. An earlier study promoted the hypothesis for the studies in this thesis, namely that chicken ovalbumin upstream promoter transcription factor-II (COUP-TFII) might constitute such a marker, as inducible knockout of COUP-TFII in pre-pubertal male mice results in failure of adult Leydig cells to develop. Therefore, the hypothesis which was explored in this thesis was that 'fetal programming' of COUP-TFII+ adult Leydig progenitor cells prior to their differentiation into adult Leydig cells, would explain how fetal events could predetermine adult testosterone levels. To investigate whether adult Leydig cells (ALC) develop from COUP-TFII+ interstitial cells, firstly an adult Leydig cell ablation/regeneration model was used, which involved a single injection of ethane dimethane sulphonate (EDS). This identified that in rats, ALC derive from COUP-TFII+ interstitial cells which do not express any other phenotypical adult Leydig or interstitial cell markers prior to differentiation. Secondly, COUP-TFII+ adult Leydig progenitor cells are abundant in the fetal testis and conserved across species, including man. Thirdly, fetal interstitial cells which differentiated into ALC, as evident from an ALC lineage tracer model, also expressed COUP-TFII. Overall, these findings suggest that the COUP-TFII+ interstitial cells which differentiate into ALC are 'adult Leydig progenitor cells'. The findings from this thesis also show that the identified adult Leydig progenitor cells express the androgen receptor (AR) in fetal life. Furthermore, experimental reduction of androgen action in fetal life in transgenic mice (AR knockout) or chemical manipulations to reduce fetal testosterone levels (di(n-butyl) phthalate; DBP exposure) resulted in a similar reduction (~40%) in progenitor cell numbers from birth through…
Subjects/Keywords: 612.6; adult Leydig stem/progenitor cells; compensated Leydig cell failure
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Export
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APA (6th Edition):
Kilcoyne, K. (2014). Early life programming of adult Leydig cell function. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/9533
Chicago Manual of Style (16th Edition):
Kilcoyne, Karen. “Early life programming of adult Leydig cell function.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed March 07, 2021.
http://hdl.handle.net/1842/9533.
MLA Handbook (7th Edition):
Kilcoyne, Karen. “Early life programming of adult Leydig cell function.” 2014. Web. 07 Mar 2021.
Vancouver:
Kilcoyne K. Early life programming of adult Leydig cell function. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1842/9533.
Council of Science Editors:
Kilcoyne K. Early life programming of adult Leydig cell function. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/9533
University of Toronto
18.
Lin, Alexander.
The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration.
Degree: PhD, 2017, University of Toronto
URL: http://hdl.handle.net/1807/79690
► The freshwater flatwormâ Schmidtea mediterranea, commonly known as the planarianâ displays remarkable feats of regeneration. Planarians amputated into fragments are capable replacing all their missing…
(more)
▼ The freshwater flatwormâ Schmidtea mediterranea, commonly known as the planarianâ displays remarkable feats of regeneration. Planarians amputated into fragments are capable replacing all their missing tissues and restore proper proportion and scale within a two weeks. Previous work has provided foundational understanding into the regulators of planarian
stem cells and the molecules that are required for repatterning and scaling; however, it remains unknown how these two seemingly disparate processes are integrated. My aim was to understand how Hippo signaling, a universal regulator of growth control across metazoans, may be integral in planarian homeostasis and regeneration by regulating
stem cell maintenance, differentiation, and patterning. Prior to my work, no one had characterized this pathway in planarians. I found that Yorkie (vertebrate homolog YAP and paralog TAZ), the effector of the Hippo signaling cascade, has roles in patterning the excretory system and anterior-posterior axis, and restricting
stem cell proliferation. My results also demonstrate that Yorkie is a crucial node in the integration of the injury responses of proliferation, apoptosis, injury-induced transcription, and patterning to coordinate regeneration and proper scaling of tissues.
Advisors/Committee Members: Pearson, Bret J, Molecular and Medical Genetics.
Subjects/Keywords: Adult Homeostasis; Hippo Signaling; Planarian; Regeneration; Stem Cells; Yorkie; 0758
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APA ·
Chicago ·
MLA ·
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Lin, A. (2017). The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/79690
Chicago Manual of Style (16th Edition):
Lin, Alexander. “The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration.” 2017. Doctoral Dissertation, University of Toronto. Accessed March 07, 2021.
http://hdl.handle.net/1807/79690.
MLA Handbook (7th Edition):
Lin, Alexander. “The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration.” 2017. Web. 07 Mar 2021.
Vancouver:
Lin A. The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1807/79690.
Council of Science Editors:
Lin A. The Pleiotropic Roles of Yorkie in Planarian Homeostasis and Regeneration. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/79690
University of Toronto
19.
Fatt, Michael Patrick.
Regulation and Repair of Neural Stem Cells and the Neurogenic Niche.
Degree: PhD, 2017, University of Toronto
URL: http://hdl.handle.net/1807/80862
► In the adult mammalian brain, numerous complex regulatory networks exist in order to regulate adult neural precursor cell (NPC) maintenance throughout life. While many of…
(more)
▼ In the
adult mammalian brain, numerous complex regulatory networks exist in order to regulate
adult neural precursor cell (NPC) maintenance throughout life. While many of these networks have been described, others remain less well understood. Here, we have asked about three of these pathways (specifically the p53 family, cellular senescence, and AMPK), using genetic and pharmacological tools to determine their roles in precursor maintenance and neurogenesis in vivo. First, we show that p53, p63, and p73 functionally interact in NPCs to regulate cell fate. When these interactions are perturbed due to combined p63;p73 heterozygosity, precursor pools and neurogenesis are rapidly depleted due to an increase in p53-mediated senescence. Second, we demonstrate that senescent NPCs rapidly accumulate in the subgranular zone (SGZ) with age, and this coincides with a decrease in neurogenesis and precursor numbers. When senescent
cells in the SGZ are reduced either pharmacologically or genetically, neurogenesis and
stem cell proliferation are dramatically enhanced, demonstrating a cell non-autonomous regulatory network between senescent and non-senescent precursors in the hippocampus. Last, we show that AMPK agonist metformin acts on two distinct pathways to regulate cell fate in
adult neural precursors. Specifically, we demonstrate that metformin acts to enhance NPC proliferation and self-renewal via a TAp73-dependent mechanism. However, metformin can also promote NPC differentiation by activating an aPKC-CBP pathway, indicating that AMPK plays an important role in regulating cell fate decisions. Taken together, the results of this thesis demonstrate that complex regulatory networks including the p53 family, cellular senescence and AMPK act to maintain
adult NPCs, and manipulation of these networks can drastically alter neurogenesis and precursor pools in vivo.
Advisors/Committee Members: Miller, Freda D, Medical Science.
Subjects/Keywords: Adult Neurogenesis; Metformin; Neural Stem Cells; p53; Senescence; 0317
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APA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fatt, M. P. (2017). Regulation and Repair of Neural Stem Cells and the Neurogenic Niche. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/80862
Chicago Manual of Style (16th Edition):
Fatt, Michael Patrick. “Regulation and Repair of Neural Stem Cells and the Neurogenic Niche.” 2017. Doctoral Dissertation, University of Toronto. Accessed March 07, 2021.
http://hdl.handle.net/1807/80862.
MLA Handbook (7th Edition):
Fatt, Michael Patrick. “Regulation and Repair of Neural Stem Cells and the Neurogenic Niche.” 2017. Web. 07 Mar 2021.
Vancouver:
Fatt MP. Regulation and Repair of Neural Stem Cells and the Neurogenic Niche. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1807/80862.
Council of Science Editors:
Fatt MP. Regulation and Repair of Neural Stem Cells and the Neurogenic Niche. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/80862
University of Cambridge
20.
Andersson Rolf, Amanda.
Application and development of advanced genetic tools to study adult stem cells.
Degree: PhD, 2018, University of Cambridge
URL: https://doi.org/10.17863/CAM.22688
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744786
► In adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate among the endodermal tissues. The harsh luminal environment of the GI tract necessitates…
(more)
▼ In adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate among the endodermal tissues. The harsh luminal environment of the GI tract necessitates replenishment of epithelial cells to maintain organ structure and function during routine turnover and injury repair. This delicate balance between gain and loss of cells is called tissue homeostasis, and multipotent tissue specific adult stem cells serve as the continuous source of self-renewal. Due to their important contribution to homeostatic maintenance the proliferative capacity of the stem cells needs to be tightly controlled, as an imbalance can result in diverse pathologies such as cancer or insufficient injury repair. Despite the crucial role for regulatory processes the molecular mechanisms and the genes governing these processes remain poorly understood. Rnf43 and its paralogue Znrf3 (RZ) act as tumour suppressors in the intestine, but their role in the gastric epithelium has not been previously investigated. Using a novel unpublished stomach specific CreERT2 expressing mouse line I found that simultaneous knockout of RZ (RZ DKO) result in gastric hyperplasia of the corpus epithelium. Gastric RZ DKO organoids show independence from the essential growth factor Rspondin-1 but require exogenous Wnt. A similar exogenous Wnt dependence was identified in a human gastric cancer cell line harbouring homozygous Rnf43 inactivating mutations. Thus, Wnt secretion inhibition might provide a new treatment paradigm for a subset of patients carrying Rnf43 mutations. The prominent role of the E3s Rnf43 and Znrf3 in the intestinal and gastric epithelial led to the question of whether other E3s either closely related to RZ or specifically expressed in stem or niche cells could play a role in homeostatic regulation, specifically in the small intestine. Using a retroviral overexpression screen I identified Rnf24 and Rnf122, two E3s that rendered intestinal organoids insensitive to withdrawal of the BMP inhibitor Noggin. Moreover, potential substrate candidates located at the cell surface membrane were identified and the generation of in vivo models initiated to provide a basis for further studies investigating the role of these E3s. In trying to address the function of the abovementioned genes using in vitro functional genetics I identified gaps in the current technology for organoid genetic engineering. I therefore developed two gene editing methods; a gRNA concatemer system allowing simultaneous knockout of multiple genes and CRISPR-FLIP enabling generation of conditional gene knockouts In summary, this thesis describes the first stomach specific knockout of Rnf43 and Znrf3 in the gastric epithelium, showing that it results in gastric hyperplasia located to the corpus epithelium. The dependence of the Rnf43 and Znrf3 knockout epithelium on exogenous Wnt signalling provides a potential treatment strategy for a subset of patients harbouring Rnf43 mutations. Next, it identifies Rnf24 and Rnf122 as E3 ubiquitin ligases involved in intestinal stem cell…
Subjects/Keywords: 571.6; CRISPR; organoids; adult stem cells; gastrointestinal tract
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APA (6th Edition):
Andersson Rolf, A. (2018). Application and development of advanced genetic tools to study adult stem cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.22688 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744786
Chicago Manual of Style (16th Edition):
Andersson Rolf, Amanda. “Application and development of advanced genetic tools to study adult stem cells.” 2018. Doctoral Dissertation, University of Cambridge. Accessed March 07, 2021.
https://doi.org/10.17863/CAM.22688 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744786.
MLA Handbook (7th Edition):
Andersson Rolf, Amanda. “Application and development of advanced genetic tools to study adult stem cells.” 2018. Web. 07 Mar 2021.
Vancouver:
Andersson Rolf A. Application and development of advanced genetic tools to study adult stem cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2018. [cited 2021 Mar 07].
Available from: https://doi.org/10.17863/CAM.22688 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744786.
Council of Science Editors:
Andersson Rolf A. Application and development of advanced genetic tools to study adult stem cells. [Doctoral Dissertation]. University of Cambridge; 2018. Available from: https://doi.org/10.17863/CAM.22688 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744786
University of Louisville
21.
Wang, Meng.
Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease.
Degree: PhD, 2011, University of Louisville
URL: 10.18297/etd/1513
;
https://ir.library.louisville.edu/etd/1513
► Human adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs have been…
(more)
▼ Human
adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs have been developed in our laboratory. In response to morphogens, the hONPs differentiate along several neural lineages. This study optimized conditions for the differentiation of hONPs towards dopaminergic neurons. The hONPs were treated with Sonic Hedgehog, in the presence or absence of Retinoic acid and/or forskolin. Transcription factors (Nurrl, Pitx3 and Lmxla) that promote embryonic mouse or chicken dopaminergic development were employed to determine if they would modulate lineage restriction of these
adult human progenitors. Transcription factor expression and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, were detected in the transfected
cells after 4-month selection with G418, indicating transfected hONPs were stably restricted towards a dopaminergic lineage. Furthermore, enzyme immunoassay was employed to detect the synthesis and release of dopamine. The most efficient dopamine transfection paradigm was determined. Equivalent levels of several neurotrophic factors were detected in both the pre- and post-transfected hONPs which have potential roles in the maintenance, survival and proliferation of dopaminergic neurons. This study engrafted
cells modified by the most efficient transfection paradigm for dopamine formation into a unilateral neurotoxin, 6-hydroxydopamine (6-OHDA)-induced Parkinsonian rat model. Thirty-five percent of the animals engrafted with hONPs had improved behavioral recovery as demonstrated by the amphetamine induced rotation test as well as a comer preference and cylinder paw preference, over a period of more than 24 weeks. No difference was observed between the pre- and post-transfected groups indicating that the host environment facilitated dopaminergic differentiation in situ. Human fibroblasts did not diminish the Parkinsonian rotational deficits at any point during the study. The engrafted hONP population remained intact and TH positive for a minimum of six months in vivo. Higher dopamine leveis were detected in the striatum of behaviorally recovered animals than in equivalent regions of their non-recovered counterparts. Throughout these experiments, no evidence of tumorigenicity was observed. These studies support our hypothesis that human
adult olfactory epithelial-derived progenitors represent a unique autologous cell type for a cell-based strategy for the treatment of Parkinson's disease.
Advisors/Committee Members: Roisen, Fred J..
Subjects/Keywords: Olfactory epithelium; Parkinson's disease; Adult stem cells; Dopamine
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APA ·
Chicago ·
MLA ·
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CSE |
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APA (6th Edition):
Wang, M. (2011). Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1513 ; https://ir.library.louisville.edu/etd/1513
Chicago Manual of Style (16th Edition):
Wang, Meng. “Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease.” 2011. Doctoral Dissertation, University of Louisville. Accessed March 07, 2021.
10.18297/etd/1513 ; https://ir.library.louisville.edu/etd/1513.
MLA Handbook (7th Edition):
Wang, Meng. “Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease.” 2011. Web. 07 Mar 2021.
Vancouver:
Wang M. Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease. [Internet] [Doctoral dissertation]. University of Louisville; 2011. [cited 2021 Mar 07].
Available from: 10.18297/etd/1513 ; https://ir.library.louisville.edu/etd/1513.
Council of Science Editors:
Wang M. Human olfactory epithelial-derived progenitors : a potential source for cell therapy for Parkinson's disease. [Doctoral Dissertation]. University of Louisville; 2011. Available from: 10.18297/etd/1513 ; https://ir.library.louisville.edu/etd/1513
University of New South Wales
22.
Pandit, Sonali.
Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss.
Degree: Garvan Institute of Medical Research, 2011, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/51616
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10283/SOURCE02?view=true
► The main goals of this thesis are:• To investigate the survival of adult human olfactory stem cells xenotransplanted into a mouse model of early-onset hearing…
(more)
▼ The main goals of this thesis are:• To investigate the survival of
adult human olfactory
stem cells xenotransplanted into a mouse model of early-onset hearing loss (A/J mice). • To evaluate the ability of the
stem cells to rescue hearing in early-onset progressive sensorineural hearing loss. The main results of this thesis are:• Xenotransplanted
adult human olfactory
stem cells survived for 4 weeks after the surgery (end point of the study).• The
stem cells were mainly found in perilymphatic compartments of the cochlea (scala vestibuli and scala tympani) while only a few
stem cells were present in scala media.• The
stem cells did not integrate into cochlear tissues.• Post-surgery hearing threshold levels in
stem cell-transplanted mice were found to be significantly lower than threshold levels of sham-injected mice (P < .05) for both click and pure tone stimuli. In addition, the threshold shift (difference between pre and post-surgery hearing thresholds) was significantly less in the
stem cell transplanted animals than the sham-injected animals for click stimulus. Overall,
adult human olfactory
stem cell transplantation can help preserve hearing during early-onset sensorineural hearing loss.This improvement in hearing could be due to paracrine effect of
adult human olfactory
stem cells.
Advisors/Committee Members: Oleskevich, Sharon, Garvan Institute of Medical Research, Faculty of Medicine, UNSW.
Subjects/Keywords: Adult human olfactory stem cells; Early onset sensorineural hearing loss
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APA (6th Edition):
Pandit, S. (2011). Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/51616 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10283/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Pandit, Sonali. “Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss.” 2011. Masters Thesis, University of New South Wales. Accessed March 07, 2021.
http://handle.unsw.edu.au/1959.4/51616 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10283/SOURCE02?view=true.
MLA Handbook (7th Edition):
Pandit, Sonali. “Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss.” 2011. Web. 07 Mar 2021.
Vancouver:
Pandit S. Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss. [Internet] [Masters thesis]. University of New South Wales; 2011. [cited 2021 Mar 07].
Available from: http://handle.unsw.edu.au/1959.4/51616 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10283/SOURCE02?view=true.
Council of Science Editors:
Pandit S. Xenotransplantation of adult human olfactory stem cells into mice with early-onset sensorineural hearing loss. [Masters Thesis]. University of New South Wales; 2011. Available from: http://handle.unsw.edu.au/1959.4/51616 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10283/SOURCE02?view=true
University of Cambridge
23.
Rimland, Casey.
Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.
Degree: PhD, 2019, University of Cambridge
URL: https://doi.org/10.17863/CAM.33331
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763807
► The biliary tree is a series of ductular tissues responsible for the drainage of bile produced by the liver and pancreatic secretions from the pancreas.…
(more)
▼ The biliary tree is a series of ductular tissues responsible for the drainage of bile produced by the liver and pancreatic secretions from the pancreas. The biliary tree is affected by a diversity of life- threatening diseases collectively called cholangiopathies. Cholangiopathies show regionalization, with some diseases such as biliary atresia predominantly targeting extrahepatic bile ducts (EHBDs) outside of the liver. Despite this, little is known on whether anatomical location within the biliary tree contributes to differences in functionality of biliary epithelium, especially in the EHBD compartment. Additionally, reports have demonstrated the possibility for in vitro culture of bile duct stem/progenitor cell organoids from both intrahepatic (IHBD) and EHBD sources. The relation of these organoid systems to each other, and to their tissue of origin, is largely unknown. In this dissertation, I address these major questions by combining transcriptional analyses and in vitro culture of human bile duct organoids derived from primary IHBD and EHBD epithelium. First, I show that in vitro organoids can be derived from four regions of the human biliary tree: gallbladder, common bile duct, pancreatic duct, and intrahepatic bile ducts. Characterization of these organoids demonstrated expression of adult stem cell (LGR5/PROM1) and ductal (KRT19/KRT7) markers suggesting these cultures contained cells with a biliary stem/progenitor phenotype. Further, I show that IHBD organoids are distinct from EHBD organoids requiring different conditions for sustained growth. Using RNA-Sequencing, I demonstrate that primary tissues from different regions of the extrahepatic biliary tree display unique expression profiles and identify novel tissue-specific markers. I also show that only a limited number of these tissue specific differences are maintained in the in vitro organoids and that the organoids are very different from their tissue of origin. Finally, I demonstrate that IHBD, but not EHBD organoids, express a low-level of hepatocyte-specific markers under differentiation conditions. Taken together, the work in this dissertation has uncovered regional specific markers for different anatomical regions of the human biliary tree. Further, I demonstrate that major differences exist between IHBD organoids and EHBD organoids in vitro and discover that only IHBD organoids have the capacity to express hepatocyte markers under differentiation conditions. Ultimately, these results may help to identify new targets for therapeutic development for cholangiopathies and regenerative medicine. They have also provided important insight to the understanding of both basic biliary physiology and also the field of biliary stem/progenitor cell organoids.
Subjects/Keywords: 612.3; Biliary Tree; Extrahepatic Bile Duct; Organoids; Adult Stem Cells
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MLA ·
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Manager
APA (6th Edition):
Rimland, C. (2019). Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.33331 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763807
Chicago Manual of Style (16th Edition):
Rimland, Casey. “Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 07, 2021.
https://doi.org/10.17863/CAM.33331 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763807.
MLA Handbook (7th Edition):
Rimland, Casey. “Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids.” 2019. Web. 07 Mar 2021.
Vancouver:
Rimland C. Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 07].
Available from: https://doi.org/10.17863/CAM.33331 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763807.
Council of Science Editors:
Rimland C. Understanding regional diversity in the human biliary tree through transcriptomic profiling of primary tissues and in vitro derived organoids. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.33331 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763807
University of Lund
24.
Devaraju, Karthikeyan.
Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts.
Degree: 2014, University of Lund
URL: https://lup.lub.lu.se/record/4330891
;
https://portal.research.lu.se/ws/files/3826268/4333830.pdf
► Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain…
(more)
▼ Stroke is a major cause of death and disability
around the world. Stroke leads to loss of neurons and also other
cells in the brain due to lack of blood supply. Currently no
therapies are available to treat stroke-related disability. It has
been shown that stroke leads to increased neurogenesis, birth of
new neurons, within the brain. This increased neurogenesis is not
sufficient to restore lost function. There is a need to develop
therapies for neuronal replacement by improving neurogenesis within
the brain and / or transplanting neurons. Cortical strokes lead to
more disability after stroke as compared to those affecting the
striatum, and whether cortical neurogenesis occurs after stroke is
controversial. Cell transplantation may be the key to cortical
repair after stroke. Reports have identified positive but very few
negative regulators of neurogenesis after stroke, and suggested
that ependymal cells can also contribute to stroke-induced
neurogenesis. Transplantation of neurons generated from different
sources such as fetal brain, embryonic stem cells and induced
pluripotent stem cells are associated with ethical issues and carry
the risk of immune rejection and tumorigenicity. Direct conversion
of patient’s own skin cells to neurons could overcome these
problems and potentially restore function after transplantation in
stroke-damaged brain. In this thesis we have used transgenic
models, viral vectors, electroporation-mediated gene delivery and
overexpression of transcription factors to demonstrate neurogenesis
from neural stem cells, ependymal cells in the lateral ventricular
wall and fibroblasts. We show that Lnk, a known inhibitor of
hematopoietic stem cell self-renewal, is also expressed in the
brain. Overexpression or removal of Lnk expression leads to
decreased or increased neurogenesis in vitro respectively. When
brain is damaged by stroke there is increased proliferation of
neural stem cells in animals without Lnk expression. This was not
observed in status epilepticus, a severe form of epilepsy. We
determined that upregulation of Stat1/3 after stroke leads to
increased Lnk expression. Subsequently Lnk inhibits cellular
response to increased IGF1 stimulation after stroke, by decreasing
Akt phosphorylation. We have identified Lnk signaling as a novel
mechanism of influencing neurogenic response to stroke. We next
determined if ependymal cells in lateral ventricular wall of adult
rat brain contribute to neurogenesis after stroke. We identified
FoxJ1 as a marker of ependymal cells in rats similar to mice, and
used FoxJ1 promoter in piggyBac system to genetically label these
cells with fluorescent reporter proteins GFP or RFP by
electroporation. Tracing the lineage of the labeled cells in intact
and stroke-damaged brain, we identified that FoxJ1 expressing cells
contribute to olfactory bulb neurogenesis while the striatal
neurogenic response was not significant. Thus, FoxJ1 expressing
cells probably have only a minor role in repair after stroke. We
then tested whether human fetal lung fibroblasts could be…
Subjects/Keywords: Neurology; adult neurogenesis; stroke; neural stem cells; Lnk; ependymal cells; FoxJ1; cortical reprogramming
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Manager
APA (6th Edition):
Devaraju, K. (2014). Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/4330891 ; https://portal.research.lu.se/ws/files/3826268/4333830.pdf
Chicago Manual of Style (16th Edition):
Devaraju, Karthikeyan. “Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts.” 2014. Doctoral Dissertation, University of Lund. Accessed March 07, 2021.
https://lup.lub.lu.se/record/4330891 ; https://portal.research.lu.se/ws/files/3826268/4333830.pdf.
MLA Handbook (7th Edition):
Devaraju, Karthikeyan. “Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts.” 2014. Web. 07 Mar 2021.
Vancouver:
Devaraju K. Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts. [Internet] [Doctoral dissertation]. University of Lund; 2014. [cited 2021 Mar 07].
Available from: https://lup.lub.lu.se/record/4330891 ; https://portal.research.lu.se/ws/files/3826268/4333830.pdf.
Council of Science Editors:
Devaraju K. Neurogenesis from Neural Stem Cells, Ependymal Cells and
Fibroblasts. [Doctoral Dissertation]. University of Lund; 2014. Available from: https://lup.lub.lu.se/record/4330891 ; https://portal.research.lu.se/ws/files/3826268/4333830.pdf
University of Toronto
25.
Doherty, James Patrick.
The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell.
Degree: 2009, University of Toronto
URL: http://hdl.handle.net/1807/17427
► Neural stem cells (NSCs) in the adult forebrain are thought to comprise a subpopulation of cells that express glial fibrillary acidic protein (GFAP), termed B…
(more)
▼ Neural stem cells (NSCs) in the adult forebrain are thought to comprise a subpopulation of cells that express glial fibrillary acidic protein (GFAP), termed B cells. These GFAP+ cells generate proliferating neuroblasts that migrate from the lateral ventricle subependyma along the rostral migratory stream to become olfactory bulb interneurons. Based on this lineage, we set out to create a NSC deficient mouse through targeted ablation of dividing GFAP+ cells in vivo. We successfully depleted the GFAP+ cells as seen using an in vitro colony forming assay in multiple kill paradigms, however we were unable to permanently eliminate the multipotent, self-renewing colony forming cells. Instead, the targeted ablation of GFAP+ cells revealed an upstream, GFAP- cell that was induced to proliferate in the presence of leukemia inhibitory factor (LIF). These findings support the hypothesis that a population of GFAP-, LIF responsive cells are the definitive adult NSC upstream of GFAP+ cells.
MAST
Advisors/Committee Members: Morshead, Cindi M., Medical Science.
Subjects/Keywords: Adult neural stem cells; Neuroscience; Neural stem cells; 0317
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APA (6th Edition):
Doherty, J. P. (2009). The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/17427
Chicago Manual of Style (16th Edition):
Doherty, James Patrick. “The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell.” 2009. Masters Thesis, University of Toronto. Accessed March 07, 2021.
http://hdl.handle.net/1807/17427.
MLA Handbook (7th Edition):
Doherty, James Patrick. “The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell.” 2009. Web. 07 Mar 2021.
Vancouver:
Doherty JP. The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell. [Internet] [Masters thesis]. University of Toronto; 2009. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1807/17427.
Council of Science Editors:
Doherty JP. The Isolation and Identification of the Definitive Adult Neural Stem Cell Following Ablation of the Neurogenic GFAP Expressing Subependymal Cell. [Masters Thesis]. University of Toronto; 2009. Available from: http://hdl.handle.net/1807/17427
Washington State University
26.
[No author].
INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
.
Degree: 2011, Washington State University
URL: http://hdl.handle.net/2376/2856
► Spermatogonial stem cells (SSCs) are the only adult stem cell population capable of transmitting genetics to offspring and accomplish this feat through the production of…
(more)
▼ Spermatogonial
stem cells (SSCs) are the only
adult stem cell population capable of transmitting genetics to offspring and accomplish this feat through the production of spermatozoa. Indeed, spermatogenesis yields a virtually unlimited supply of gametes throughout the lifespan of the male as a result of coordinated SSC differentiation and self-renewal. In essence, SSCs are the keepers of the male germ-line and this population originates from primitive germ cell lineages during neonatal life in a species-specific manner. SSCs, like other
adult stem cells, are thought to reside in a niche microenvironment that must be established and maintained in the seminiferous tubules of the neonatal and
adult testis. Extrinsic signals produced by somatic
cells within the niche act to direct the cell fate of SSCs by either supporting self-renewal or initiating differentiation leading to meiotic entry and production of spermatozoa. Despite the importance of these processes, little is known about the biochemical and cellular mechanisms that govern SSC homeostasis and identity due to the lack of SSCs specific biomarkers and complex cell biology of the testis. These challenges underscore the importance of functional
stem cell transplantation for investigating the role of endocrine and locally produced factors that regulate the biological activity of SSCs. Moreover, donor-derived spermatogenesis after transplantation is the only reliable and accurate means to identify a bonafide SSC in a cell population and assay SSC self-renewal in response
Advisors/Committee Members: McLean, Derek J (advisor).
Subjects/Keywords: Animal Sciences;
Physiology;
Developmental Biology;
Adult Stem Cells;
Gamete Biology;
Growth Factors;
Spermatogenesis;
Spermatogonial Stem Cells;
Testis
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APA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2011). INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/2856
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
.” 2011. Thesis, Washington State University. Accessed March 07, 2021.
http://hdl.handle.net/2376/2856.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
.” 2011. Web. 07 Mar 2021.
Vancouver:
author] [. INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
. [Internet] [Thesis]. Washington State University; 2011. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/2376/2856.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. INVESTIGATION OF FACTORS REGULATING SPERMATOGONIAL STEM CELL HOMEOSTASIS IN THE MAMMALIAN TESTIS
. [Thesis]. Washington State University; 2011. Available from: http://hdl.handle.net/2376/2856
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
27.
Flores, Aimee Alyssa.
Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells.
Degree: Molecular Biology, 2018, UCLA
URL: http://www.escholarship.org/uc/item/4936t5nd
► For an increasing number of cancers, the cell of origin has been demonstrated to be theresident adult stem cell. One such cancer is squamous cell…
(more)
▼ For an increasing number of cancers, the cell of origin has been demonstrated to be theresident adult stem cell. One such cancer is squamous cell carcinoma, for which recentstudies in our lab traced its origin to the hair follicle stem cells. Malignant transformationis thought to coincide with a dramatic shift towards the use of glycolysis and establishmentof a ‘Warburg’ state – increased metabolism of glucose to lactate. How the Warburg Effectis established during tumor initiation and progression in vivo remains unclear. The currentconsensus is that the bulk of the energy generated in most adult tissue cells is created byoxidative phosphorylation, while more highly proliferative cells, such as activated immunecells and cells transformed to make a tumor, mainly use glycolysis. Little is knownabout how individual cell types generate energy in vivo, however, and how theirmetabolism influences basic cell fate decisions such as cell division, migration ordifferentiation. Using genetically engineered mouse models that allow the study of both tissuehomeostasis and the Warburg Effect in vivo, I have made important observations thatprovide the basis for new investigations into the role of metabolism in key cell fatedecisions by adult stem cells. In this dissertation I present data indicating that hair folliclestem cells possess a unique metabolic profile that may be critical for their maintenanceand for their response to oncogenic insults. Importantly, they suggest the possibility thatthe “Warburg Effect” is the result of the expansion of an already glycolytic subpopulation,namely the hair follicle stem cells.
Subjects/Keywords: Molecular biology; Cellular biology; Developmental biology; Adult Stem Cells; Cancer Metabolism; Cellular Metabolism; Hair Follicle Stem Cells
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APA (6th Edition):
Flores, A. A. (2018). Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/4936t5nd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Flores, Aimee Alyssa. “Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells.” 2018. Thesis, UCLA. Accessed March 07, 2021.
http://www.escholarship.org/uc/item/4936t5nd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Flores, Aimee Alyssa. “Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells.” 2018. Web. 07 Mar 2021.
Vancouver:
Flores AA. Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells. [Internet] [Thesis]. UCLA; 2018. [cited 2021 Mar 07].
Available from: http://www.escholarship.org/uc/item/4936t5nd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Flores AA. Investigating the Role of Metabolism in Tissue Homeostasis and Tumor Initiation by Hair Follicle Stem Cells. [Thesis]. UCLA; 2018. Available from: http://www.escholarship.org/uc/item/4936t5nd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
National University of Ireland – Galway
28.
O'Sullivan, Janice.
Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
.
Degree: 2013, National University of Ireland – Galway
URL: http://hdl.handle.net/10379/3588
► Osteoarthritis (OA) is a chronic disease of joints characterised by progressive destruction of articular cartilage resulting in painful, limited joint movement. Cartilage has a limited…
(more)
▼ Osteoarthritis (OA) is a chronic disease of joints characterised by progressive
destruction of articular cartilage resulting in painful, limited joint movement.
Cartilage has a limited ability to self-repair due to low chondrocyte motility and
proliferative rates, and is further complicated by the absence of blood vessels for
recruitment of circulating
cells. Current clinical therapies do not result in full
regeneration of healthy cartilage tissue. The long-term success of cartilage repair
will therefore depend on regenerative methodologies resulting in the restoration of
articular cartilage that closely duplicates the native tissue. For cell-based therapies,
the optimal cell source must be readily accessible with easily isolated, abundant
cells capable of collagen type II and sulfated proteoglycan production in
appropriate proportions. Although a cell source with these therapeutic properties
remains elusive, mesenchymal
stem cells (MSCs) show promise of reproducing the
structural or biomechanical properties of healthy articular cartilage. Current
knowledge of and selection techniques for chondroprogenitors within the MSC
population are relatively limited. This study focuses on methods for their isolation
and activation.
As cartilage is a tissue composed primarily of extracellular matrix (ECM)
surrounding chondrocytes, it was hypothesised that there is a sub-population of
progenitor
cells in bone marrow that are primed towards the chondrogenic
pathway with pre-requisite receptors for extracellular matrix (ECM) molecules.
Consequently, chondroprogenitors could be isolated from bone marrow via their
specific adhesion to cartilaginous ECM proteins. In this study hyaluronan (HA) and
chondroitin-6-sulfate (CS) were used to select
cells directly from bone marrow by
coating tissue culture plastic or by adding in solution to unprocessed marrow.
Various methods were undertaken to isolate this putative population of
chondroprogenitors such as isolating the early adherent (EA) and late adherent (LA)
cells and the sub-populations present as slow adherent
cells in the EA and LA
marrow fractions. Extracellular matrix-mediated isolation of
cells, specifically the exposure of MSCs to a specific ECM molecule adhered to tissue culture plastic and
subsequent re-plating onto non-coated flasks resulted in a 9-fold higher
chondrogenic ability compared to the traditionally isolated plastic adhered
cells.
These ECM isolated
cells retained their tri-lineage potential but the increase in
differentiation potential was a chondrogenic phenomenon only. Further analysis
suggested that this was not a specific selection of chondroprogenitors but an
activation of a chondro-specific pathway within the ECM isolated MSCs. This study
has not only elucidated a process enabling the isolation of a highly chondrogenic
population of
cells but also a process of MSC isolation from marrow that enables
the retrieval of a higher yield of
cells than is typically isolated using traditional
methods.
Advisors/Committee Members: Barry, Frank (advisor), Murphy, Mary (advisor), Coleman, Cynthia (advisor).
Subjects/Keywords: Adult Stem Cells;
Osteoarthritis;
Mesenchymal Stem Cells;
Cartilage regeneration;
Regenerative Medicine;
Cartilagenous extracellular matrix;
Hyaluronic Acid;
Regenerative Medicine Institute (REMEDI)
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
O'Sullivan, J. (2013). Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
. (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/3588
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
O'Sullivan, Janice. “Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
.” 2013. Thesis, National University of Ireland – Galway. Accessed March 07, 2021.
http://hdl.handle.net/10379/3588.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
O'Sullivan, Janice. “Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
.” 2013. Web. 07 Mar 2021.
Vancouver:
O'Sullivan J. Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
. [Internet] [Thesis]. National University of Ireland – Galway; 2013. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/10379/3588.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
O'Sullivan J. Glycosaminoglycan Dependent Isolation of Mesenchymal Chondroprogenitor Populations from Human Bone Marrow
. [Thesis]. National University of Ireland – Galway; 2013. Available from: http://hdl.handle.net/10379/3588
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Rochester
29.
McClelland, Lindy; Jasper, Heinrich.
Role of Tis11 in Drosophila Intestinal Stem Cell
Function.
Degree: PhD, 2016, University of Rochester
URL: http://hdl.handle.net/1802/30696
► Many tissues contain a population of adult stem cells whose function is precisely regulated to promote tissue homeostasis. Tissues whose stem cells fail to respond…
(more)
▼ Many tissues contain a population of adult stem
cells whose function is precisely regulated
to promote tissue
homeostasis. Tissues whose stem cells fail to respond to
regenerative cues
atrophy, while stem cells that are continuously
proliferating can promote hyperproliferative
diseases. Therefore,
an understanding of the precise regulation of adult stem cell
function will lead
to insights on how these adult stem cells
function to maintain healthy tissues.
Many adult stem cells
exhibit a proliferative plasticity where their proliferation rates
dynamically increase in response to damage to their resident
tissue. For these adult stem cells, a
critical part of maintaining
tissue homeostasis is the reacquisition of basal proliferation
rates after
the tissue has been repaired. Currently, little is
known about the molecular mechanisms that
promote the restoration
of basal proliferation rates.
Here I show that Tis11, an
Adenine-uridine Rich Element (ARE) binding protein that
promotes
mRNA degradation, is required to re-establish basal proliferation
rates in the Drosophila
intestinal epithelium after regenerative
episodes. Through lineage tracing techniques and detailed
kinetic
studies of the ISC regenerative response, I find Tis11 functions
cell autonomously to limit
ISC proliferation. I also find that
Tis11 is dynamically regulated, as its expression and activity is
increased in ISCs during tissue repair. Furthermore, promoting
defects in mRNA stability
independent of Tis11 activity also
limits ISC proliferation rates. This observation along with the
finding that clone size of Tis11 gain-of-function ISCs can be
rescued by simultaneously making
them deficient in RNA degradation
support that Tis11 is functioning in ISCs by promoting mRNA
decay.
Based on transcriptome and RNA immunoprecipitation data, I propose
that Tis11 activation
represents an integral part of a negative
feedback mechanism that limits the expression of several
components of pro-mitotic signaling pathways. Our results identify
Tis11 mediated mRNA decay
as a new, evolutionarily conserved
mechanism of re-establishing the basal proliferation rates of
stem
cells in regenerating tissues.
Subjects/Keywords: Adult stem cells; Tissue homeostasis; Reaquisition of quiescence; Post-transciptional gene regulation; Tis11
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
McClelland, Lindy; Jasper, H. (2016). Role of Tis11 in Drosophila Intestinal Stem Cell
Function. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/30696
Chicago Manual of Style (16th Edition):
McClelland, Lindy; Jasper, Heinrich. “Role of Tis11 in Drosophila Intestinal Stem Cell
Function.” 2016. Doctoral Dissertation, University of Rochester. Accessed March 07, 2021.
http://hdl.handle.net/1802/30696.
MLA Handbook (7th Edition):
McClelland, Lindy; Jasper, Heinrich. “Role of Tis11 in Drosophila Intestinal Stem Cell
Function.” 2016. Web. 07 Mar 2021.
Vancouver:
McClelland, Lindy; Jasper H. Role of Tis11 in Drosophila Intestinal Stem Cell
Function. [Internet] [Doctoral dissertation]. University of Rochester; 2016. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1802/30696.
Council of Science Editors:
McClelland, Lindy; Jasper H. Role of Tis11 in Drosophila Intestinal Stem Cell
Function. [Doctoral Dissertation]. University of Rochester; 2016. Available from: http://hdl.handle.net/1802/30696
30.
Sun, Gerald Jan-Yu.
CELLULAR MECHANISMS OF ADULT NEUROGENESIS.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37196
► The adult mammalian brain possesses the remarkable capacity for generating new neurons throughout life. Adult mouse hippocampal neurogenesis is thought to recapitulate many hallmarks of…
(more)
▼ The
adult mammalian brain possesses the remarkable capacity for generating new neurons throughout life.
Adult mouse hippocampal neurogenesis is thought to recapitulate many hallmarks of neurodevelopment and occurs in a spatially-defined, temporally-dilated manner. Because the mature central nervous system context is often thought of as inhospitable to cell growth or genesis, it is important to understand how the complex
adult neurogenesis and neurodevelopmental processes can occur, and in what ways these processes may differ from those of embryonic neurogenesis. The thesis research presented here examines how
adult mouse hippocampal neurogenesis occurs at a cellular level throughout neural development from
stem cell to nerve cell. The first part of my thesis examines the regulation of cell fate decisions made by neural
stem cells to generate diverse cell types in the
adult mouse hippocampus. Under normal conditions, neural
stem cells generate
cells of only the neuronal
and astroglial lineages. However, conditional inactivation of an important negative regulator of Ras signaling, neurofibromin 1 (NF1), revealed an intrinsic capacity of
adult hippocampal neural
stem cells to generate the oligodendroglial lineage. This finding suggests a novel, non-canonical paradigm of
stem cell regulation via active limitation of
stem cell plasticity. The second part of my thesis examines how newborn neurons migrate within the
adult mouse hippocampus.
Adult-born hippocampal neurons are glutamatergic, excitatory dentate granule
cells that are thought to abide by migration rules of the developing neocortex to migrate exclusively in a radial direction away from the neurogenic niche. Using a novel system to visualize clones of neurogenic neural
stem cells and their clonal progeny, I quantitatively studied newborn neuron migration. I found that newborn neurons exhibit extensive and almost exclusive tangential migration, which utilizes direct contacts with niche
vasculature as a migration substrate. This finding represents a novel form of glutamatergic cell migration. The third part of my thesis examines how newborn neurons grow their dendrites and axons in the
adult mouse hippocampus. To date, studying axon development with single-axon resolution has been impossible due to technological limitations precluding capturing whole, intact, fine axonal processes. In collaboration with Kurt Sailor, I developed a new technology, named SEBI (serial end-block imaging), to seamlessly reconstruct large volumes of tissue and recover full, native, intact cellular structure with high resolution. Using this technology, I studied the development of newborn hippocampal granule
cells and discovered complex axonal projections and ordered lamination patterns. My findings represent the first characterization of the development and structure of the full intact, primary dendrite and axon structure for newborn hippocampal granule
cells. In summary, my thesis work
presented here has contributed significant novel discoveries in neurodevelopment in the
adult mouse…
Advisors/Committee Members: Doetzlhofer, Angelika (advisor).
Subjects/Keywords: adult neurogenesis; stem cells; neurodevelopment
…2
1.3 Adult neural stem cells of the hippocampus… …adult life. Such capacity is now known to be
conferred by adult stem cells that, in many cases… …performed to understand the regenerative capacity of adult stem
cells across many somatic tissues… …strikingly, in some cases such as the in
hematopoietic system, adult stem cells can fully and… …decades that the
mammalian adult brain—including human brains10,11—also possesses stem cells…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, G. J. (2014). CELLULAR MECHANISMS OF ADULT NEUROGENESIS. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37196
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sun, Gerald Jan-Yu. “CELLULAR MECHANISMS OF ADULT NEUROGENESIS.” 2014. Thesis, Johns Hopkins University. Accessed March 07, 2021.
http://jhir.library.jhu.edu/handle/1774.2/37196.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sun, Gerald Jan-Yu. “CELLULAR MECHANISMS OF ADULT NEUROGENESIS.” 2014. Web. 07 Mar 2021.
Vancouver:
Sun GJ. CELLULAR MECHANISMS OF ADULT NEUROGENESIS. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Mar 07].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37196.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sun GJ. CELLULAR MECHANISMS OF ADULT NEUROGENESIS. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37196
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
◁ [1] [2] [3] [4] ▶
. 
Open Access Theses and Dissertations
