You searched for subject:(Cell differentiation).
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1.
Mori, Megumi.
Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells.
Degree: Department of Molecular Biology, Cell Biology and
Biochemistry, 2018, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:792693/ 
► Embryonic stem cells (ESCs) are found early in the developing embryo and from this initial population, all cells in the body are eventually derived. A…
(more)
▼ Embryonic stem cells (ESCs) are found early in the
developing embryo and from this initial population, all cells in
the body are eventually derived. A hallmark characteristic of ESCs
is their pluripotent nature, which is established to a large extent
by transcriptional regulation. The core transcription factor
network commonly referred to in stem
cell pluripotency includes
Oct3/4, Sox2 and Nanog which then contribute to a vast protein
interaction network. The process by which embryonic stem cells
become differentiated into cells with novel characteristics is
tightly regulated and specific. In the past several decades, there
has been great interest regarding how mammalian ESCs might be
cultured in vitro to promote the derivation of
cell types for
research as well as medical endeavors. Primordial germ cells, the
precursors of gametes, are an especially interesting
subject for
differentiation as they are linked to ESCs via their reinstated
pluripotency upon fertilization to divide and constitute a new
organism. This thesis describes the theory and experimental
methodology necessary to derive primordial germ
cell-like cells
(PGCLCs) from mouse embryonic stem cells (ESCs). Throughout this
process, the optimal expansion and culture conditions of ESCs,
epiblast-like cells (EpiLCs) and PGCLCs were implemented. A major
initial goal was to assess the efficacy of
differentiation via
expected changes in gene expression throughout each
differentiation
step. Establishing this in vitro model system will then allow us to
answer mechanistic questions about the how subunits of the core
transcription factor TFIID complex may contribute to the
maintenance of ESC pluripotency through the transcriptional network
and how they change to regulate the pathway by which PGCLCs are
specified.
Advisors/Committee Members: Freiman, Richard (Advisor).
Subjects/Keywords: Cell differentiation
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APA (6th Edition):
Mori, M. (2018). Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792693/
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):
Mori, Megumi. “Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells.” 2018. Thesis, Brown University. Accessed February 26, 2020.
https://repository.library.brown.edu/studio/item/bdr:792693/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mori, Megumi. “Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells.” 2018. Web. 26 Feb 2020.
Vancouver:
Mori M. Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells. [Internet] [Thesis]. Brown University; 2018. [cited 2020 Feb 26].
Available from: https://repository.library.brown.edu/studio/item/bdr:792693/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mori M. Gene Expression Changes Associated with the Differentiation
of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like
Cells. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792693/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Irofuala, Chinedu.
Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine.
Degree: Biomedical Engineering, 2018, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:792817/
► Cardiovascular diseases are some of the most common and most lethal diseases in the world. On top of that, the only treatment option available that…
(more)
▼ Cardiovascular diseases are some of the most common
and most lethal diseases in the world. On top of that, the only
treatment option available that would allow for cardiovascular
function to be restored to healthy levels long-term is a heart
transplant. Not only are heart transplants difficult to come by –
the waiting list is almost double the number of hearts available
each year – but even this solution may require life-long
immunosuppressant and drug use. By instead using regenerative
medicine and tissue engineering, it is possible to create
innovative solutions using human induced pluripotent stem
cell
derived cardiomyocytes that may create a pathway towards restoring
functionality to damaged hearts. Furthermore, these cardiomyocytes
can be used to perform extensive cardiotoxicity testing in human
cells, providing a more accurate and appropriate medium for
assessing the implications of new drugs heading to market, as well
as how a patient’s heart may react to a prescribed drug regimen.
Currently, one of the largest barriers to these fields of research
is the large number of pure cardiomyocytes that must be produced to
meet the demands of academia and industry. This is the motivation
behind the work presented here, which aims to optimize the
cardiomyocyte
differentiation process of the GiPSC, NCRM-5, and
WTC-11 human induced pluripotent stem
cell lines by altering
seeding density and Chiron concentration. It is shown that high
seeding density (137,000 cells per well) and low Chiron (3 µM)
concentration produce the highest purity cardiomyocytes regardless
of lineage, but that the level of purity is dictated by the genetic
background of the
cell type. As tissue engineering and regenerative
medicine move closer to personalized medicine approaches, it
becomes increasingly important to understand the implications of
genetics in determining the
differentiation potential of a
patient’s own induced pluripotent stem cells for therapy and
treatment purposes.
Advisors/Committee Members: Coulombe, Kareen (Advisor), Shukla, Anita (Reader), Dawson, Michelle (Reader).
Subjects/Keywords: Cell differentiation
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APA (6th Edition):
Irofuala, C. (2018). Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792817/
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):
Irofuala, Chinedu. “Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine.” 2018. Thesis, Brown University. Accessed February 26, 2020.
https://repository.library.brown.edu/studio/item/bdr:792817/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Irofuala, Chinedu. “Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine.” 2018. Web. 26 Feb 2020.
Vancouver:
Irofuala C. Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine. [Internet] [Thesis]. Brown University; 2018. [cited 2020 Feb 26].
Available from: https://repository.library.brown.edu/studio/item/bdr:792817/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Irofuala C. Cardiac Differentiation Potential is Modulated by Genetic
Background: Implications for Personalized Medicine. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792817/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Oxford
3.
Iber, Dagmar.
From single cells to multicellular organisms : a quantitative analysis.
Degree: 2006, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:2717597c-8bb3-4fcc-9887-cae30844c5b5
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437035
► The evolution and development of multicellular organisms requires cells to differentiate, interact and "collaborate". Our understanding of the molecular mechanisms is still hazy. In this…
(more)
▼ The evolution and development of multicellular organisms requires cells to differentiate, interact and "collaborate". Our understanding of the molecular mechanisms is still hazy. In this dissertation mathematical modelling is used to integrate available experimental data and to make testable predictions about such mechanisms. The thesis is split into three parts, each of which addresses one of the three challenges: differentiation, adhesion and collaboration. In the first part, a mathematical model is developed to explain how, in the absence of polarizing cues from the environment, sister cells with identical genomes can follow distinct routes of differentiation. It is shown that difference in cell size, resulting from asymmetric cell division, is sufficient to induce differential cell fate in Bacillus subtilis. The model predicts that this effect depends on the allosteric behaviour of a kinase and the low catalytic rate of the corresponding phosphatase; both properties were subsequently confirmed in experiments. During the development of multicellular organisms, differentiation can arise in response to gradients. By example of dorso-ventral patterning it is shown how a shallow maternal gradient can be converted into a sharp pattern. In the second part, a model for cell adhesion via integrins is developed, and it is shown that, for physiological parameters, binding of a ligand and of a stabilizing factor such as talin are insufficient for ligand-dependent integrin activation, and that a positive signaling feedback is required. In the final part, antibody affinity maturation is studied as an example for division of labour between collaborating cells. A novel B cell selection mechanism, based on competition for T cell help rather than for antigen, is proposed and shown to reconcile heretofore inexplicable experimental observations. Such a mechanism requires B cells to discriminate among different affinities of binding, and it is further shown that this can be achieved if B cell signaling is initiated by antigen-dependent receptor-inhibitor segregation. The predictions of the model match experimental measurements quantitatively.
Subjects/Keywords: 571.6; Cell differentiation : Cell adhesion : Cell interaction
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APA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Iber, D. (2006). From single cells to multicellular organisms : a quantitative analysis. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:2717597c-8bb3-4fcc-9887-cae30844c5b5 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437035
Chicago Manual of Style (16th Edition):
Iber, Dagmar. “From single cells to multicellular organisms : a quantitative analysis.” 2006. Doctoral Dissertation, University of Oxford. Accessed February 26, 2020.
http://ora.ox.ac.uk/objects/uuid:2717597c-8bb3-4fcc-9887-cae30844c5b5 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437035.
MLA Handbook (7th Edition):
Iber, Dagmar. “From single cells to multicellular organisms : a quantitative analysis.” 2006. Web. 26 Feb 2020.
Vancouver:
Iber D. From single cells to multicellular organisms : a quantitative analysis. [Internet] [Doctoral dissertation]. University of Oxford; 2006. [cited 2020 Feb 26].
Available from: http://ora.ox.ac.uk/objects/uuid:2717597c-8bb3-4fcc-9887-cae30844c5b5 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437035.
Council of Science Editors:
Iber D. From single cells to multicellular organisms : a quantitative analysis. [Doctoral Dissertation]. University of Oxford; 2006. Available from: http://ora.ox.ac.uk/objects/uuid:2717597c-8bb3-4fcc-9887-cae30844c5b5 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437035
University of Georgia
4.
Mao, Chen.
Characterization of 3-D collagen gels for functional cell-based biosensing.
Degree: MS, Biological Engineering, 2001, University of Georgia
URL: http://purl.galileo.usg.edu/uga_etd/mao_chen_200112_ms
► To address the need for cell-based functional information towards accelerated drug discovery, we proposed a three-dimensional, cell-based matrix made by immobilizing IMR-32 neuroblastoma cells in…
(more)
▼ To address the need for
cell-based functional information towards accelerated drug discovery, we proposed a three-dimensional,
cell-based matrix made by immobilizing IMR-32 neuroblastoma cells in collagen hydrogels. The feasibility of this matrix for functional assays was investigated with respect to mechanical, optical and biocompatibility properties. The collagen gels exhibited mechanical and optical properties suitable for
cell-based biosensing. Using fluorescence confocal imaging, morphological differences were observed between monolayer (2-D) and collagen entrapped (3-D) cells. However, no differences in proliferation were observed. Both 2-D and 3-D cells failed to develop a resting membrane potential typical of motor neurons. 3-D entrapped cells exhibited a difference in depolarization-induced calcium influx, suggesting differences in expression of voltage-dependent calcium channels. These studies constitute a first step towards establishing functional
cell-based assays in hydrogel matrices.
Advisors/Committee Members: William Kisaalita.
Subjects/Keywords: Cell differentiation
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APA (6th Edition):
Mao, C. (2001). Characterization of 3-D collagen gels for functional cell-based biosensing. (Masters Thesis). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/mao_chen_200112_ms
Chicago Manual of Style (16th Edition):
Mao, Chen. “Characterization of 3-D collagen gels for functional cell-based biosensing.” 2001. Masters Thesis, University of Georgia. Accessed February 26, 2020.
http://purl.galileo.usg.edu/uga_etd/mao_chen_200112_ms.
MLA Handbook (7th Edition):
Mao, Chen. “Characterization of 3-D collagen gels for functional cell-based biosensing.” 2001. Web. 26 Feb 2020.
Vancouver:
Mao C. Characterization of 3-D collagen gels for functional cell-based biosensing. [Internet] [Masters thesis]. University of Georgia; 2001. [cited 2020 Feb 26].
Available from: http://purl.galileo.usg.edu/uga_etd/mao_chen_200112_ms.
Council of Science Editors:
Mao C. Characterization of 3-D collagen gels for functional cell-based biosensing. [Masters Thesis]. University of Georgia; 2001. Available from: http://purl.galileo.usg.edu/uga_etd/mao_chen_200112_ms
University of Hong Kong
5.
赵伟玮; Zhao, Weiwei.
Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis.
Degree: PhD, 2017, University of Hong Kong
URL: http://hdl.handle.net/10722/244289
► Currently, osteoarthritis (OA) is recognized as a heterogeneous disease with a variety of causes. The initiation and progression of OA cannot be accounted for by…
(more)
▼ Currently, osteoarthritis (OA) is recognized as a
heterogeneous disease with a variety of causes. The initiation and
progression of OA cannot be accounted for by mechanical stress
alone. There is an increasing body of evidence showing that
systemic conditions, such as chronic inflammation and metabolic
disorders, contribute to the development of OA. Given the high
frequency of OA’s co-occurrence with cardiovascular diseases (CVDs)
and metabolic syndrome (MetS), special attention has been paid to
studying the common mechanisms underlying those systemic diseases.
Unraveling the common biological pathways would benefit our
understanding of the pathogenesis of metabolic OA as well as the
development of novel drugs for OA treatment.
The view that
endothelin-1 (ET-1) plays a critical role in the cardiovascular
system arose from a number of observations that levels of plasma
ET-1 were found to be significantly upregulated in patients with
CVDs and MetS. More recently, it was suggested that ET-1 promoted
cartilage degradation via collagenase upregulation. Thereby, we
hypothesized that the alteration of systemic ET-1 would affect the
vascular functions as well as the cartilage homeostasis. In this
study, we aimed to investigate the role of ET-1 in chondrocyte
differentiation and cartilage homeostasis.
The predominant
expression of ET-1 in hypertrophic chondrocytes was detected,
suggesting the association of ET-1 signaling with chondrocyte
hypertrophy. The overexpression of endothelial ET-1 resulted in
slight dwarfism in neonatal mice, which was attributed to the
activity of ET-1 in endochondral ossification initiated by the
hypertrophic differentiation of chondrocytes. Age-related
spontaneous cartilage degeneration was found in transgenic mice
overexpressing endothelial ET-1 (TET-1 mice), suggesting that the
elevation of systemic ET-1 affected the homeostasis of articular
cartilage. An increased number of type Ⅹ collagen positive
chondrocytes in un-calcified cartilage was identified. Furthermore,
accelerated progression of traumatic OA was observed in TET-1 mice.
In vitro study showed that ET-1 facilitated chondrocyte hypertrophy
by increasing the expression of hypertrophic markers. These results
suggested increased ET-1 promoted cartilage degeneration probably
via the regulation of chondrocyte hypertrophy.
Taken together, we
have demonstrated the role of systemic ET-1 in chondrocyte
hypertrophy, endochondral ossification, cartilage maintenance, and
OA. This is the first in vivo study to investigate the effect of
elevated systemic ET-1 on chondrocytes and cartilage, contributing
to the knowledge about ET-1’s role in the skeletal
system.
published_or_final_version
Orthopaedics and Traumatology
Doctoral
Doctor of Philosophy
Subjects/Keywords: Cartilage cells; Cell differentiation; Endothelins
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APA ·
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CSE |
Export
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Manager
APA (6th Edition):
赵伟玮; Zhao, W. (2017). Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis. (Doctoral Dissertation). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/244289
Chicago Manual of Style (16th Edition):
赵伟玮; Zhao, Weiwei. “Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis.” 2017. Doctoral Dissertation, University of Hong Kong. Accessed February 26, 2020.
http://hdl.handle.net/10722/244289.
MLA Handbook (7th Edition):
赵伟玮; Zhao, Weiwei. “Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis.” 2017. Web. 26 Feb 2020.
Vancouver:
赵伟玮; Zhao W. Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis. [Internet] [Doctoral dissertation]. University of Hong Kong; 2017. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/10722/244289.
Council of Science Editors:
赵伟玮; Zhao W. Role of endothelin-1 in chondrocyte differentiation and
cartilage homeostasis. [Doctoral Dissertation]. University of Hong Kong; 2017. Available from: http://hdl.handle.net/10722/244289
University of Hong Kong
6.
Lu, Xibin.
Quantitative characterization of mouse embryonic stem
cell state transition.
Degree: PhD, 2014, University of Hong Kong
URL: Lu,
X.
[盧希彬].
(2014).
Quantitative
characterization
of
mouse
embryonic
stem
cell
state
transition.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b5351003
;
http://dx.doi.org/10.5353/th_b5351003
;
http://hdl.handle.net/10722/221529
► It is known that on-and-off transcription factors (TFs) regulations play crucial roles in differentiation and reprogramming. Oct4, Sox2 and Nanog as well as their constituted…
(more)
▼ It is known that on-and-off transcription factors
(TFs) regulations play crucial roles in differentiation and
reprogramming. Oct4, Sox2 and Nanog as well as their constituted
gene networks cooperatively maintain ES cell pluripotency.
Recently, TFs such as Nanog, Stella and Rex1 show heterogeneous
expression in ES cell populations and such heterogeneity lead to
different differentiation potential indicating that heterogeneous
gene expression may control cell fate. Besides gene regulation
triggered by TFs, intrinsic noise was also found to be a potential
source in heterogeneity and stochastic cell fate determination. For
safe clinical application of stem cell-based therapy, it is crucial
to quantify these dynamic processes and transition rate during
research and development. However, in most cases, the transition
rate is too low to be measured and is often entangled with cell
proliferation. In order to disentangle these processes, we
established a Nanog-EGFP reporter ES cell line and quantified the
transition rates between two subpopulations. We also developed a
mathematical model involving cell state transition, proliferation
and noise to facilitate deciphering this process.
We first
generated a dual reporter ES cell line (Nanog-EGFP and
EF1α-H2B-mCherry) based on PiggyBac system. Using a simple ES cell
differentiation process, differentiation and dedifferentiation
could be obviously observed based on Nanog ES cell reporter. In
order to quantify the transition and proliferation rate, we
performed multiple batches of ES cell differentiation and
dedifferentiation based with this reporter ES cell line.
Mathematical models (drift-diffusion-growth equation) are also
introduced to fit the data. The quantitative and nontrivial model
predictions lead to new experiments and hypotheses. Combined the
flow cytometry data with mathematical models, we are able to
directly derive the most likely potential landscape (Waddington’s
landscape) based on Nanog distribution. Our results and approaches
developed would provide more clues for future ES cell
differentiation studies.
In another project, we generated
multiple ES cell reporters in which Nanog, Oct4 and Rex1 were all
labeled with different fluorescence proteins. We differentiated the
reporter ES cell line specifically into epiblast stem cell (EpiSC)
based on previous protocols. Based on flow cytometry analysis, we
found that, during the transition from ES cell to EpiSC state, all
the three marker genes showed heterogeneous expression pattern, and
three sub-populations can be identified at the EpiSC steady (later)
state. The cell fate identity and potential converting ability into
other identities like ES cell or inter-converting ability among
three populations were being conducted based on chemical factors.
In addition, we quantitatively characterized PiggyBac mediated
multiplex gene transfer in mouse embryonic stem cell which lay a
good foundation in above mentioned ES cell reporter generation. HS4
insulator was also characterized on the effect of protecting from
promoter…
Subjects/Keywords: Cell differentiation; Stem cells
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APA ·
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Manager
APA (6th Edition):
Lu, X. (2014). Quantitative characterization of mouse embryonic stem
cell state transition. (Doctoral Dissertation). University of Hong Kong. Retrieved from Lu, X. [盧希彬]. (2014). Quantitative characterization of mouse embryonic stem cell state transition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5351003 ; http://dx.doi.org/10.5353/th_b5351003 ; http://hdl.handle.net/10722/221529
Chicago Manual of Style (16th Edition):
Lu, Xibin. “Quantitative characterization of mouse embryonic stem
cell state transition.” 2014. Doctoral Dissertation, University of Hong Kong. Accessed February 26, 2020.
Lu, X. [盧希彬]. (2014). Quantitative characterization of mouse embryonic stem cell state transition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5351003 ; http://dx.doi.org/10.5353/th_b5351003 ; http://hdl.handle.net/10722/221529.
MLA Handbook (7th Edition):
Lu, Xibin. “Quantitative characterization of mouse embryonic stem
cell state transition.” 2014. Web. 26 Feb 2020.
Vancouver:
Lu X. Quantitative characterization of mouse embryonic stem
cell state transition. [Internet] [Doctoral dissertation]. University of Hong Kong; 2014. [cited 2020 Feb 26].
Available from: Lu, X. [盧希彬]. (2014). Quantitative characterization of mouse embryonic stem cell state transition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5351003 ; http://dx.doi.org/10.5353/th_b5351003 ; http://hdl.handle.net/10722/221529.
Council of Science Editors:
Lu X. Quantitative characterization of mouse embryonic stem
cell state transition. [Doctoral Dissertation]. University of Hong Kong; 2014. Available from: Lu, X. [盧希彬]. (2014). Quantitative characterization of mouse embryonic stem cell state transition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5351003 ; http://dx.doi.org/10.5353/th_b5351003 ; http://hdl.handle.net/10722/221529
University of Saskatchewan
7.
Rudulier, Christopher.
CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype.
Degree: 2011, University of Saskatchewan
URL: http://hdl.handle.net/10388/ETD-2011-12-282
► The Th1/Th2 phenotype of the immune response generated against a pathogen or disease can have a profound impact upon the survival of the host. Thus,…
(more)
▼ The Th1/Th2 phenotype of the immune response generated against a pathogen or disease can have a profound impact upon the survival of the host. Thus, a complete and accurate model for the generation of Th1 versus Th2 cells is critical for the development of effective immunotherapeutic strategies aimed against diseases including cancer and tuberculosis.
Numerous factors are considered to be important in the differential development of Th1 and Th2 cells. These include the strength of stimulation through the T
cell receptor, the cytokine environment, the dose of antigen, and the types of co-stimulatory molecules expressed by the antigen-presenting cells presenting the T cell’s cognate antigen. A common thread found in the majority of studies on the generation of Th1 and Th2 cells is that naïve CD4+ T cells are thought to be passive players in this process. In contrast, our laboratory has demonstrated, in a number of in vivo systems, that the density of the responding naïve CD4+ T cells, that is to say the frequency of responding CD4+ T cells in an animal, has a significant impact on their Th1/Th2 phenotype. In particular, our laboratory has reported that in response to antigen, a low density of responding naïve CD4+ T cells give rise to Th1 cells while a high density of responding CD4+ T cells give rise to Th2 cells. Although we have made these observations, we had not, prior to the work described herein, elucidated the mechanism(s) surrounding this phenomenon. This was the impetus for the experiments detailed in this thesis.
In order to investigate the mechanism(s) mediating the effect that the density of responding CD4+ T cells has on the Th1/Th2 phenotype, we have developed an in vitro system that employs a physiological number of naïve TCR transgenic CD4+ T cells (DO11.10) specific for the OVA323-339 peptide in the context of I-Ad. My observations in this in vitro system mirror
previous in vivo observation in that a low frequency of naïve CD4+ DO11.10 T cells cultured with syngeneic APC and the OVA323-339 peptide, acquire a Th1 phenotype while naïve CD4+ DO11.10 T cells cultured at high frequencies, under identical conditions, acquire a Th2 phenotype.
By controlling the type of APC in our culture system, we have ascertained that the effect of CD4+ T
cell density on the differential generation of Th1 and Th2 cells is mediated by B cells, but not dendritic cells. We also found that the addition of an agonistic anti-CD28 antibody skews the phenotype of T cells cultured at low densities towards the Th2 pole while partially blocking of CD80 and CD86, through the addition of CTLA4-Ig to high density T
cell cultures, resulted in the development of Th1 cells. In contrast, modulating the interactions between CD40/CD40L and OX40/OX40L, two co-stimulatory molecule/ligand pairs known to affect Th1/Th2
differentiation, through the addition of agonistic and antagonistic antibodies in high or low density CD4+ T
cell cultures did not alter the Th1/Th2 phenotype of the newly activated DO11.10 T cells. Thus, it appears…
Advisors/Committee Members: Bretscher, Peter, Havele, Calliopi, Gerdts, Volker, Bull, Harold, Goldie, Hughes.
Subjects/Keywords: CD4 T cell differentiation
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Manager
APA (6th Edition):
Rudulier, C. (2011). CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2011-12-282
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):
Rudulier, Christopher. “CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype.” 2011. Thesis, University of Saskatchewan. Accessed February 26, 2020.
http://hdl.handle.net/10388/ETD-2011-12-282.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rudulier, Christopher. “CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype.” 2011. Web. 26 Feb 2020.
Vancouver:
Rudulier C. CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype. [Internet] [Thesis]. University of Saskatchewan; 2011. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/10388/ETD-2011-12-282.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rudulier C. CD4+ T cell interactions through CD28/B7 molecules affects their Th1/Th2 phenotype. [Thesis]. University of Saskatchewan; 2011. Available from: http://hdl.handle.net/10388/ETD-2011-12-282
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Central Connecticut State University
8.
Banda, Erin.
Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification.
Degree: Department of Biomolecular Sciences, 2010, Central Connecticut State University
URL: http://content.library.ccsu.edu/u?/ccsutheses,1569
► The ability of embryonic stem cells to give rise to all cells comprising the three germ layers – endoderm, mesoderm and ectoderm – highlights a…
(more)
▼ The ability of embryonic stem cells to give rise to all cells comprising the three germ layers – endoderm, mesoderm and ectoderm – highlights a powerful in vivo system for the study of early embryonic development. Human embryonic stem
cell (hESC) derived- neural stem cells (NSCs) provide a means for understanding development of the mammalian nervous system as well as neurodegenerative diseases associated with atypical development and disease pathology of the nervous system. Here I demonstrate identification of the earliest neural stem
cell gene expressed during in vitro NSC specification. In this study, Musashi1 (Msi1), a member of the Notch signaling pathway, has interestingly been identified as the earliest NSC marker expressed during monolayer
differentiation of hESCs towards NSC fates. Notch signaling is well classified in its role for maintenance of NSC populations in vivo, as well as in vitro, but this early Msi1 expression suggests that Notch signaling may have a role in specification of early neurectodermal cells. The identification of the earliest NSC gene in vivo allows the possibility of the development of a hESC-derived NSC reporter line, capable of highlighting cells as they become allocated to the neural lineage. Additionally, purification of these early NSCs allows for the study and transplantation of purified NSC populations, without contaminating ESCs or other proliferative
cell types capable of forming teratocarcinomas.
Advisors/Committee Members: Mulrooney, James P;.
Subjects/Keywords: Cell differentiation; Embryonic stem cells
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APA (6th Edition):
Banda, E. (2010). Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification. (Thesis). Central Connecticut State University. Retrieved from http://content.library.ccsu.edu/u?/ccsutheses,1569
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):
Banda, Erin. “Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification.” 2010. Thesis, Central Connecticut State University. Accessed February 26, 2020.
http://content.library.ccsu.edu/u?/ccsutheses,1569.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Banda, Erin. “Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification.” 2010. Web. 26 Feb 2020.
Vancouver:
Banda E. Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification. [Internet] [Thesis]. Central Connecticut State University; 2010. [cited 2020 Feb 26].
Available from: http://content.library.ccsu.edu/u?/ccsutheses,1569.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Banda E. Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification. [Thesis]. Central Connecticut State University; 2010. Available from: http://content.library.ccsu.edu/u?/ccsutheses,1569
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Ottawa
9.
Kocharyan, Avetik.
Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
.
Degree: 2018, University of Ottawa
URL: http://hdl.handle.net/10393/37517
► Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder associated with premature aging in various tissues and organs of the afflicted individuals, including accelerated skeletal…
(more)
▼ Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder associated with premature aging in various tissues and organs of the afflicted individuals, including accelerated skeletal muscle atrophy. Classical HGPS manifests due to single-base substitution in the LAMNA gene which encodes Lamin A/C proteins. As a result of the mutation, a truncated form of Lamin (known as Progerin) is produced which undergoes persistent farnesylation during post-translational modification. Accumulation of Progerin in the nucleus has been linked to various cellular abnormalities including abnormal nuclear morphologies and altered chromatin organization, among others. However, the exact molecular mechanisms leading to skeletal muscle atrophy have not yet been elucidated. In this study, the iPSC approach was implemented in order to study the skeletal muscle phenotype of HGPS by generating and characterizing a population of Pax7 positive skeletal muscle precursor cells (SMPs).
During the course of this project, we have demonstrated the need for excessive optimization of the previously developed directed differentiation protocol for successful application on induced Pluripotent Stem Cells. Furthermore, we have successfully modified the protocol to allow for a more rapid expansion of the SMPs through regular passaging of the myogenic cells starting on day 20 of differentiation. Additionally, this new method produced more uniform distribution of the myogenic cells and allowed for successful freezing/thawing of the myogenic cells.
When compared to the controls, the HGPS-derived SMPs did not appear to be defective in formation, proliferation or differentiation. Abnormal nuclear morphology and DNA damage, documented in HGPS fibroblasts and vascular smooth muscle cells, were not detected the in myogenic cells. Furthermore, we were not able to detect Progerin protein accumulation in the generated myogenic cultures, offering an explanation for the absence of these phenotypes in the skeletal muscle system.
Subjects/Keywords: Muscle;
Stem cell;
Progeria;
Differentiation
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APA (6th Edition):
Kocharyan, A. (2018). Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37517
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):
Kocharyan, Avetik. “Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
.” 2018. Thesis, University of Ottawa. Accessed February 26, 2020.
http://hdl.handle.net/10393/37517.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kocharyan, Avetik. “Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
.” 2018. Web. 26 Feb 2020.
Vancouver:
Kocharyan A. Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
. [Internet] [Thesis]. University of Ottawa; 2018. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/10393/37517.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kocharyan A. Derivation and Characterization of Pax7 Positive Skeletal Muscle Precursor Cells from Control and HGPS-derived induced Pluripotent Stem Cells
. [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37517
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Harvard University
10.
Weinreb, Caleb.
Gene Expression Dynamics in Single Cells.
Degree: PhD, 2019, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42013156
► Dynamic regulation of gene expression is central to fate choice and differentiation. Genes drive changes in cell state and also serve as markers of mature…
(more)
▼ Dynamic regulation of gene expression is central to fate choice and differentiation. Genes drive changes in cell state and also serve as markers of mature cell types and immature intermediates. Advances in single-cell RNA-seq (scSeq) have made it possible measure the expression of thousands of genes in tens of thousands of cells in a single experiment. Single-cell RNA sequencing (scSeq) opens up a new terrain in the study of differentiation and fate choice, but it has an important limitation: existing methods kill cells in the process of measurement, and thus prevent following a cell’s state over time. The inability to track cells prevents a full understanding of the dynamic events that accompany differentiation, or how variation in the state of progenitor cells predisposes their sub- sequent fate choices. These limitations are particularly evident in hematopoiesis – the process of steady-state blood production in bone marrow. scSeq is increasingly used to characterize the heterogeneity of hematopoietic stem and progenitor cells, but the functional consequences of this heterogeneity have been difficult to ascertain. Here, several methods are described for inferring single-cell gene expression dynamics. Chapter 1 presents a visualization method called SPRING that facilitates human inference of dynamics. A more direct approach to infer dynamics from high dimensional data is described in chapter 2 based on the principle of population balance. This analysis also highlights several properties of gene expression dynamics that cannot be inferred from a single-cell snapshot, including: whether unmeasured variables contribute significantly to fate choice; the degree to which cells in the same gene expression state also have the same velocity in their state; and where fate commitment occurs in gene expression space. Chapter 3 describes an experimental approach for tracking cell state over time that involves clonally marking cells, letting them divide, measuring one sister right away, and measuring the other sister later on. Applied to hematopoiesis, this method partially addresses the questions raised in Chapter 2, demonstrating the existence of hidden variables during differentiation and mapping fate probability across the gene expression landscape. It also opens up new directions for perturbational analysis of hematopoietic fate choice, and may pave the way for linking cell state and fate in other systems.
Systems Biology
Advisors/Committee Members: Mitchison, Timothy (advisor), Singer, Meromit (committee member), Camargo, Fernando (committee member).
Subjects/Keywords: Single-cell; dynamic inference; differentiation
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Weinreb, C. (2019). Gene Expression Dynamics in Single Cells. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42013156
Chicago Manual of Style (16th Edition):
Weinreb, Caleb. “Gene Expression Dynamics in Single Cells.” 2019. Doctoral Dissertation, Harvard University. Accessed February 26, 2020.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42013156.
MLA Handbook (7th Edition):
Weinreb, Caleb. “Gene Expression Dynamics in Single Cells.” 2019. Web. 26 Feb 2020.
Vancouver:
Weinreb C. Gene Expression Dynamics in Single Cells. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2020 Feb 26].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42013156.
Council of Science Editors:
Weinreb C. Gene Expression Dynamics in Single Cells. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42013156
University of Texas Southwestern Medical Center
11.
Shields, Benjamin Baker.
Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1589
► Recent undertakings to identify the genetic lesions associated with ovarian cancer have noted the striking diversity of mutations occurring in this disease. This genetic diversity…
(more)
▼ Recent undertakings to identify the genetic lesions associated with ovarian cancer have noted the striking diversity of mutations occurring in this disease. This genetic diversity has complicated the search for novel therapies. However, recent data has suggested that one commonality of ovarian tumors might be ablation of miRNA biogenesis. Here I conducted a broad-scale gain-of-function microRNA (miRNA) screen in 16 ovarian cancer
cell lines to annotate the functional landscape present in such a chaotic genetic background. miRNAs function as multigenic perturbations allowing for interrogation of maximal gene space with few experiments. This screen identified multiple miRNAs reducing
cell viability with the majority of hits being toxic in only one or two lines screened. This surprising finding reflected the commonality of altered miRNA function in ovarian tumors while also suggesting that specifics of this alteration in function are unique to each tumor. To investigate more public vulnerabilities, I focused mechanistic studies on miRNAs displaying penetrance in greater than 5
cell lines. miR-517a reduced
cell viability in over 30% of the panel and also reduced tumor burden in vivo. Functional analysis of the predicted targets of miR-517a revealed that expression of this miRNA reduced protein levels of ARCN1, a member of the coatamer complex, and that knockdown of ARCN1 reduced
cell viability similar to miR-517a. Another penetrant miRNA, miR-124a, reduced
cell viability in 37.5% of the panel and functional analysis of this miRNA revealed it promoted a
cell differentiation program. Analysis of predicted targets revealed that expression of miR-124a reduced expression the homeodomain transcription factor SIX4, resulting in increased signaling along the tumor suppressive AMPK pathway and epithelial
differentiation. Furthermore, SIX4 displayed increased expression in ovarian tumors and depletion of SIX4 expression reduced tumor
cell viability in vitro and in vivo. Therefore, SIX4 overexpression might function to deflect
cell differentiation in tumors. Thus, the common loss of miRNA function observed in ovarian tumors might serve to maintain an undifferentiated state, and engagement of
cell fate determination programs via re-expression of miRNAs can result in catastrophic consequences for cancer
cell viability.
Advisors/Committee Members: Castrillon, Diego H., White, Michael A., Altschuler, Steven J., Brekken, Rolf A..
Subjects/Keywords: Cell Differentiation; MicroRNAs; Ovarian Neoplasms
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shields, B. B. (2013). Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1589
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):
Shields, Benjamin Baker. “Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/2152.5/1589.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shields, Benjamin Baker. “Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.” 2013. Web. 26 Feb 2020.
Vancouver:
Shields BB. Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/2152.5/1589.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shields BB. Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1589
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
California State University – Sacramento
12.
Torres, Christian I.
Development of induced pluripotent stem cell-derived self-organizing renal organoids.
Degree: MS, Biological Sciences (Stem Cell, 2019, California State University – Sacramento
URL: http://hdl.handle.net/10211.3/212754
► Human pluripotent stem cells have the potential to serve as a model of organ development and disease when grown in a three-dimensional (3D) structure. Human…
(more)
▼ Human pluripotent stem cells have the potential to serve as a model of organ development and disease when grown in a three-dimensional (3D) structure. Human kidney development results from the reciprocal inductive interactions involving the metanephric mesenchyme (future excretory component of the kidney) and the ureteric bud (future collecting system). One of the challenges in creating kidney organoids is recapitulating the complex interactions between these primordial structures. Prior studies have shown methods to achieve either metanephric mesenchyme or ureteric bud lineage commitment from human induced pluripotent stem cells (hiPSC); however, a single protocol to achieve both lineages simultaneously is in need of further assessment. The goals of these studies were to expand a well-characterized bank of hiPSC, and to test a self-organizing
differentiation protocol to determine if commitment to metanephric mesenchyme and ureteric bud precursors could be obtained in a combined culture system using either transwells or a 3D culture system. Studies focused on evaluating directed
differentiation of hiPSC toward metanephric and ureteric bud lineages and recapitulating kidney development. The collection of cells was performed at select time points for gene expression analysis using quantitative PCR (qPCR) and at study endpoint for histologic analysis and immunohistochemistry. hiPSC were expanded and cryopreserved with characterization demonstrating pluripotency (endoderm, mesoderm, and ectoderm) by qPCR. When hiPSC were directed toward renal lineage
differentiation, gene expression studies showed upregulation of the mesodermal marker brachyury, and markers of anterior and posterior intermediate mesoderm suggesting
differentiation toward ureteric bud and metanephric mesenchyme phenotypes, respectively. Differentiated hiPSC formed tubules resembling early kidney development under both culture conditions. Analysis of renal developmental markers by immunohistochemistry showed similar expression patterns. The results of these studies support a
differentiation protocol that recapitulates early stages of renal development.
Advisors/Committee Members: Mulligan, Kimberly.
Subjects/Keywords: Directed differentiation; Stem cell; Organoids
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APA (6th Edition):
Torres, C. I. (2019). Development of induced pluripotent stem cell-derived self-organizing renal organoids. (Masters Thesis). California State University – Sacramento. Retrieved from http://hdl.handle.net/10211.3/212754
Chicago Manual of Style (16th Edition):
Torres, Christian I. “Development of induced pluripotent stem cell-derived self-organizing renal organoids.” 2019. Masters Thesis, California State University – Sacramento. Accessed February 26, 2020.
http://hdl.handle.net/10211.3/212754.
MLA Handbook (7th Edition):
Torres, Christian I. “Development of induced pluripotent stem cell-derived self-organizing renal organoids.” 2019. Web. 26 Feb 2020.
Vancouver:
Torres CI. Development of induced pluripotent stem cell-derived self-organizing renal organoids. [Internet] [Masters thesis]. California State University – Sacramento; 2019. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/10211.3/212754.
Council of Science Editors:
Torres CI. Development of induced pluripotent stem cell-derived self-organizing renal organoids. [Masters Thesis]. California State University – Sacramento; 2019. Available from: http://hdl.handle.net/10211.3/212754
Rutgers University
13.
Ambegaonkar, Abhijit Ashok, 1985-.
Regulation of planar cell polarity by the Dachsous-Fat pathway.
Degree: PhD, Cell and Developmental Biology, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/49140/
► Planar cell polarity is the polarization of cells within the plane of a tissue. The Dachsous-Fat pathway plays a key role in the regulation of…
(more)
▼ Planar cell polarity is the polarization of cells within the plane of a tissue. The Dachsous-Fat pathway plays a key role in the regulation of planar cell polarity and growth during the development of an organism. The transmembrane cadherins Fat and Dachsous from neighboring cells interact heterophilically and regulate the localization of the unconventional myosin Dachs in a cell. Four-jointed, a Golgi-localized kinase modulates the binding between Dachsous and Fat. Dachsous and Four-jointed are expressed in tissue-wide gradients, which influence Fat activity and direct the polarized membrane localization of Dachs. We demonstrate that differential expression of Dachsous or Four-jointed can modulate Dachs polarization at a distance in wing discs. This indicates that Dachsous and Four-jointed gradients can be measured over long range in a tissue through propagation of polarity. We also show that Dachsous and Fat are partially polarized along the endogenous Dachsous and Four-jointed gradients, providing a mechanism for propagation of polarity. Through directed membrane targeting of Dachs, we show that membrane localization of Dachs influences both planar cell polarity and the Hippo signaling pathway. These studies help in understanding the mechanisms involved in establishment and maintenance of planar cell polarity. The Frizzled pathway is another key pathway that regulates planar cell polarity, but its relationship with the Dachsous-Fat pathway was unclear. We demonstrate that Dachs and Dachsous can independently interact with a Frizzled pathway component, Spiny-legs, and direct its localization in vivo. Thus, the Dachsous-Fat pathway provides directional input to the Frizzled pathway by influencing the localization of Spiny-legs. These studies help in understanding how planar cell polarity is regulated in various tissues through coordination between Dachsous-Fat and Frizzled pathways. These studies also reveal that Spiny-legs and its isoform Prickle can respond to distinct planar cell polarity signals and allow the cells to compare and choose between these competing signals to direct polarity robustly in one direction. Thus, our results identify a mechanism for propagation of planar cell polarity through the tissue, establish the significance of Dachs membrane localization in Dachsous-Fat signaling and identify a molecular mechanism for crosstalk between the two planar cell polarity pathways.
Advisors/Committee Members: Grant, Barth (chair), Irvine, Kenneth (internal member), Steward, Ruth (internal member), Soto, Martha (outside member).
Subjects/Keywords: Polarity (Biology); Cell differentiation; Drosophia
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APA (6th Edition):
Ambegaonkar, Abhijit Ashok, 1. (2015). Regulation of planar cell polarity by the Dachsous-Fat pathway. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/49140/
Chicago Manual of Style (16th Edition):
Ambegaonkar, Abhijit Ashok, 1985-. “Regulation of planar cell polarity by the Dachsous-Fat pathway.” 2015. Doctoral Dissertation, Rutgers University. Accessed February 26, 2020.
https://rucore.libraries.rutgers.edu/rutgers-lib/49140/.
MLA Handbook (7th Edition):
Ambegaonkar, Abhijit Ashok, 1985-. “Regulation of planar cell polarity by the Dachsous-Fat pathway.” 2015. Web. 26 Feb 2020.
Vancouver:
Ambegaonkar, Abhijit Ashok 1. Regulation of planar cell polarity by the Dachsous-Fat pathway. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2020 Feb 26].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49140/.
Council of Science Editors:
Ambegaonkar, Abhijit Ashok 1. Regulation of planar cell polarity by the Dachsous-Fat pathway. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49140/
Penn State University
14.
Lei, Fengyang.
Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell.
Degree: PhD, Microbiology and Immunology, 2013, Penn State University
URL: https://etda.libraries.psu.edu/catalog/18747
► Cancer is one of the leading health issues that has caused tremendous impacts. Conquering cancer is imminent and finding more potent treatments to cancer is…
(more)
▼ Cancer is one of the leading health issues that has
caused tremendous impacts. Conquering cancer is imminent and
finding more potent treatments to cancer is also urgent. In
searching for novel anti-cancer regimens, recently, a new concept
of cancer immunotherapy has been proposed. It is found that by
using adoptive T cell transfer (ACT)-based immunotherapy, tumor
regression can be achieved. However, a major problem of this
strategy is the shortage of T cells for transfer. Previous work has
shown that stem cells are good candidates for generating T cell for
therapeutic purposes; however, there are many hurdles existed. The
recent discovery of the induced pluripotent stem (iPS) cell
technology hints that iPS cells are potential substitutes of
natural stem cells for generating T cells being used in cancer
immunotherapy. The hypothesis of my research is iPS cell is
identical to other stem cells in the context of T lineage
differentiation, and furthermore, iPS cell can be engineered and
induced into antigen specific T cell to bolster the tumor immune
surveillance. In the first study, it is observed iPS cells are able
to differentiate into conventional T cells after in vitro Notch
signaling pathway ligand stimulation. In vitro developed iPS cells
express general T cell markers, respond to costimulatory signal
activation and reconstitute the T cell pools of the recipient
lymphopenic mice. Following this, a second work showed
antigen-specific T cells are induced from iPS cells through the T
cell receptor (TCR) signal stimulation. In short, genetically
modifying iPS cells with antigen-specific TCR can promote the
development of corresponding T cells in vivo and developed T cells
are functional in terms of responding to antigen stimulation and
managing tumor growth. Further analyses suggested that both Notch
and TCR signals may be involved, in a synergistic manner, in
inducing iPS cells to develop into T cells; and probably, this
process is mediated by the transforming growth factor (TGF)-β
signaling pathway. These studies have initially supported our
hypothesis however both extensive and intensive studies are still
needed to further test our central hypothesis. In conclusion, my
dissertation study served as the first series of proof-of-concept
work to investigate the feasibility of an iPS cell-based,
personalized cancer immunotherapy.
Subjects/Keywords: stem cell; T cell; differentiation;
immunotherapy
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APA ·
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MLA ·
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Export
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Manager
APA (6th Edition):
Lei, F. (2013). Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/18747
Chicago Manual of Style (16th Edition):
Lei, Fengyang. “Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell.” 2013. Doctoral Dissertation, Penn State University. Accessed February 26, 2020.
https://etda.libraries.psu.edu/catalog/18747.
MLA Handbook (7th Edition):
Lei, Fengyang. “Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell.” 2013. Web. 26 Feb 2020.
Vancouver:
Lei F. Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell. [Internet] [Doctoral dissertation]. Penn State University; 2013. [cited 2020 Feb 26].
Available from: https://etda.libraries.psu.edu/catalog/18747.
Council of Science Editors:
Lei F. Development of a T cell based cancer immunotherapy by using
the induced pluripotent stem cell. [Doctoral Dissertation]. Penn State University; 2013. Available from: https://etda.libraries.psu.edu/catalog/18747
Swedish University of Agricultural Sciences
15.
Johnsson, Christoffer.
Elucidating the phytohormonal control of xylem development.
Degree: 2018, Swedish University of Agricultural Sciences
URL: https://pub.epsilon.slu.se/15386/
► Secondary xylem, commonly known as wood, has had a major impact on both our planet and civilization, its uses so ubiquitous that it is often…
(more)
▼ Secondary xylem, commonly known as wood, has had a major impact on both our planet and civilization, its uses so ubiquitous that it is often taken for granted in daily life.
New challenges imposed by growing population and changing climate have led academia and industries to search for ways of altering wood characteristics to better suit specific purposes. Achieving this by genetic engineering requires the ability to alter gene expression in specific cell types, while avoiding alterations in others. This calls for an in depth understanding of the factors directing the differentiation and development of the cell types constituting secondary xylem.
Studies detailed in this thesis exhibit my attempts to link the signals of the phytohormones auxin and gibberellic acid to the formation of fibres, and their deposition of thick secondary cell walls. Using high resolution RNA-sequencing data gathered across developing Populus wood, I was able to illustrate that the expression profiles of various wood-associated transcription factors are distinct, in relation to their functions. Furthermore, I investigated the response of gene expression and tissue anatomy to treatment by auxin and gibberellin and found that auxin down-regulates transcription factors previously identified as master regulators of fibre secondary cell wall formation, as well as impede secondary wall development on a tissue level. At the same time, gibberellic acid appears to have a general enhancing effect on the expression of the same genes, and is better able to rescue the tissue phenotype of decapitated Populus plants.
I also highlight a role for gibberellic acid in the differentiation of fibre cells through DELLA regulated interaction of Class I KNOX transcription factors with proteins of the NUCLEAR FACTOR Y family.
These findings suggest that an integration of auxin and gibberellin signals, acting through multiple pathways, is responsible for the correct spatiotemporal differentiation and development of the secondary xylem.
Subjects/Keywords: xylem; auxins; gibberellins; cell differentiation; cell walls; Xylem; Auxin; Gibberellin; differentiation; secondary cell wall
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APA (6th Edition):
Johnsson, C. (2018). Elucidating the phytohormonal control of xylem development. (Doctoral Dissertation). Swedish University of Agricultural Sciences. Retrieved from https://pub.epsilon.slu.se/15386/
Chicago Manual of Style (16th Edition):
Johnsson, Christoffer. “Elucidating the phytohormonal control of xylem development.” 2018. Doctoral Dissertation, Swedish University of Agricultural Sciences. Accessed February 26, 2020.
https://pub.epsilon.slu.se/15386/.
MLA Handbook (7th Edition):
Johnsson, Christoffer. “Elucidating the phytohormonal control of xylem development.” 2018. Web. 26 Feb 2020.
Vancouver:
Johnsson C. Elucidating the phytohormonal control of xylem development. [Internet] [Doctoral dissertation]. Swedish University of Agricultural Sciences; 2018. [cited 2020 Feb 26].
Available from: https://pub.epsilon.slu.se/15386/.
Council of Science Editors:
Johnsson C. Elucidating the phytohormonal control of xylem development. [Doctoral Dissertation]. Swedish University of Agricultural Sciences; 2018. Available from: https://pub.epsilon.slu.se/15386/
University of Cambridge
16.
Geti, Imbisaat.
Production of hepatocytes from human pluripotent stem cells for cell-based therapy.
Degree: PhD, 2019, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/291327
► Human pluripotent stem cells (hPSCs) can self-renew indefinitely in vitro while maintaining the capacity to differentiate into diverse cell types, including hepatocytes. Thus, hPSCs allow…
(more)
▼ Human pluripotent stem cells (hPSCs) can self-renew indefinitely in vitro while maintaining the capacity to differentiate into diverse cell types, including hepatocytes. Thus, hPSCs allow for large-scale production of hepatocytes necessary for cell-based therapy. Importantly, cell-based therapy involving the transplantation of hepatocytes-like cells (HLCs) represent a promising alternative to liver transplantation. However, there are two major limitations that must be overcome before hPSCs derived hepatocytes can go into clinical trials. Firstly, current protocols are not compatible with Good Manufacturing Practice (GMP) as they rely on culture media which are poorly defined and contain reagents of animal origin. Secondly, HLCs derived in vitro lack the full spectrum of adult hepatocyte functionalities and expressed foetal markers indicating that they are not equivalent to primary cells.
In this dissertation, I describe a method for generating a homogenous population of hepatocytes from hPSCs in conditions compatible with clinical applications. Furthermore, I show that the resulting GMP-like protocol is equally robust as research grade protocol to produce HLCs displaying key characteristics of their in vivo counterparts. Importantly, the efficacy of this new GMP protocol was validated in five different hPSCs lines, including three GMP grade human Embryonic Stem Cell lines. Finally, we have also characterized the resulting cells in vivo and demonstrated their safety after transplantation into immune deficient mice.
In parallel, I have optimised our protocol of differentiation by establishing a 5 steps method that closely follows liver development. For the development of this protocol, I have screened a large number of culture conditions and identified optimum time points for each step especially for hepatoblast and foetal hepatocytes stage.
Overall, the work presented in this dissertation has advanced the differentiation of hPSCs for cell-based therapy in two different ways. Firstly, it shows that production of HLCs in GMP like condition is feasible, safe and that the resulting cells could be useful for cell-based therapy in the context of liver diseases. Secondly, I have developed a new protocol with an optimised hepatoblast stage that will facilitate further clinical applications.
Subjects/Keywords: Hepatocytes; Cell based therapy; regenerative medicine; liver; liver differentiation; hepatocytes differentiation
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APA (6th Edition):
Geti, I. (2019). Production of hepatocytes from human pluripotent stem cells for cell-based therapy. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/291327
Chicago Manual of Style (16th Edition):
Geti, Imbisaat. “Production of hepatocytes from human pluripotent stem cells for cell-based therapy.” 2019. Doctoral Dissertation, University of Cambridge. Accessed February 26, 2020.
https://www.repository.cam.ac.uk/handle/1810/291327.
MLA Handbook (7th Edition):
Geti, Imbisaat. “Production of hepatocytes from human pluripotent stem cells for cell-based therapy.” 2019. Web. 26 Feb 2020.
Vancouver:
Geti I. Production of hepatocytes from human pluripotent stem cells for cell-based therapy. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2020 Feb 26].
Available from: https://www.repository.cam.ac.uk/handle/1810/291327.
Council of Science Editors:
Geti I. Production of hepatocytes from human pluripotent stem cells for cell-based therapy. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/291327
University of Toronto
17.
Soleas, John.
Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture.
Degree: PhD, 2019, University of Toronto
URL: http://hdl.handle.net/1807/97689
► Chemical and mechanical cues are known to guide the differentiation of pluripotent stem cells (PSCs) towards specific cell-types; a process known as directed differentiation. Typically,…
(more)
▼ Chemical and mechanical cues are known to guide the
differentiation of pluripotent stem cells (PSCs) towards specific
cell-types; a process known as directed
differentiation. Typically, directed
differentiation protocols to guide PSCs to specific
cell types have focused on chemical cues. For example, lung epithelial directed
differentiation protocols mimic the chemical cues observed in lung organogenesis. The products of current directed
differentiation protocols are typically unorganized cellular aggregates that are often limited by their inability to generate specific
cell types reliably. This suggests further improvements to these protocols are necessary for reliable
cell manufacturing. Introducing developmentally relevant mechanical signals offers a potentially novel strategy to improve the predictability and reduce the heterogeneity of current directed
differentiation protocols. To assess the feasibility of this concept we use polymeric substrates to guide the self-assembly of human PSC-derived lung progenitors into developmentally relevant sized tubes and assess the impact of defined architecture on
differentiation. Specifically, day 17 ventralized lung progenitors, dual positive for proximal and distal lung markers SOX2 and SOX9, respectively, were cultured in polymeric tubes with diameters of 100µm and allowed to self-assemble into cellular tubes. Cells cultured in tubes were observed to become primarily SOX9+ as compared to cells in flat cultures that remained dual positive. Cells from tube cultures were retrieved and exposed to proximal or distal airway inducing conditions. Our data show that cells from flat culture are capable of expressing proximal and distal markers under proximal and distal conditions, respectively. However, cells retrieved from tubes were able to express distal markers under distal conditions but not proximal markers under proximal conditions. Our results suggest that modulation of tension in the presence of canonical WNT signaling by culturing the dual positive cells in the 100µm tubes resulted in loss of SOX2 expression. Overall, this thesis suggests that the use of a bioinspired mechanical microenvironment to organize and control the
differentiation of developing lung epithelial populations during directed
differentiation is a tractable strategy to control cellular
differentiation in vitro.
Advisors/Committee Members: McGuigan, Alison P, Waddell, Thomas K, Biomedical Engineering.
Subjects/Keywords: Biophysical forces; Lung differentiation; Stem cell differentiation; Tissue Engineering; 0202
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MLA ·
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CSE |
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APA (6th Edition):
Soleas, J. (2019). Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/97689
Chicago Manual of Style (16th Edition):
Soleas, John. “Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture.” 2019. Doctoral Dissertation, University of Toronto. Accessed February 26, 2020.
http://hdl.handle.net/1807/97689.
MLA Handbook (7th Edition):
Soleas, John. “Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture.” 2019. Web. 26 Feb 2020.
Vancouver:
Soleas J. Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture. [Internet] [Doctoral dissertation]. University of Toronto; 2019. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1807/97689.
Council of Science Editors:
Soleas J. Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture. [Doctoral Dissertation]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/97689
ETH Zürich
18.
Borsa, Mariana.
Impact of asymmetric cell division on T cell differentiation.
Degree: 2018, ETH Zürich
URL: http://hdl.handle.net/20.500.11850/283722
► Successful immune responses rely on diversity. Being equipped with highly variable T cell receptors (TCRs), which convey antigen specificity, CD8+ T cells exhibit an immense…
(more)
▼ Successful immune responses rely on diversity. Being equipped with highly variable T
cell receptors (TCRs), which convey antigen specificity, CD8+ T cells exhibit an immense repertoire of different naïve cells even before antigen encounter, but for an immune response to be effective, both clonal expansion, and
differentiation must take place. Upon cognate antigen activation, one single naïve CD8+ T
cell can give rise to different progenies, including effector and memory cells. How this diversity is generated, is still a phenomenon incompletely elucidated, but some mechanisms were reported to be involved in fate determination, such as differential strength of TCR activation, and differential exposure to inflammatory stimuli, leading to differential transcriptional and metabolic profiles, epigenetic control of gene expression, and asymmetric
cell division (ACD).
Concerning ACD as a means to foster diversification, most studies were limited to describe the mitotic polarization of a variety of components in activated naïve T lymphocytes, leading to the rise of two daughter cells inheriting distinct potential fates. We set out to study whether the ability to undergo ACD is limited to certain CD8+ T
cell subsets and developed a strategy to modulate ACD rates. Using the murine Lymphocytic Choriomeningitis virus (LCMV) infection model, we established a correlation between ACD and cellular stemness, as naïve and memory CD8+ T cells (which exhibit stemness in terms of self-maintenance and being able to generate progenies with different fates) were found to divide asymmetrically, while terminally differentiated cells, as short-lived effector and exhausted cells, lacked this ability. ACD modulation was achieved by transient mTOR inhibition, leading to higher ACD rates in naïve and memory cells, and reestablishment of ACD in pre-terminally exhausted PD-1int CD8+ T cells. The ability to undergo ACD correlated with memory potential. Upon adoptive transfer, progenies of mTOR-inhibited LCMV-specific TCR transgenic P14 cells, exhibiting increased ACD rates, showed improved expansion upon acute or chronic LCMV infection, resulting in more efficient viral control. mTOR inhibition also led to higher ACD rates in stimulated naïve and memory human CD8+ T cells. Thus, ACD modulation might be a potential useful tool to enforce memory
differentiation in T cells.
Memory formation is known to be impaired upon aging as a consequence of profound remodelling of immune responses, in particular CD8+ T cells. This led us to investigate how aging affects the ability of CD8+ T cells from aged individuals to undergo ACD and whether transient mTOR inhibition could reinvigorate memory features that are impaired during immunosenescence. Analysis of CD8+ T cells isolated from young and old naïve P14 mice showed that aging led to overall decreased ACD rates, which could be increased upon transient mTOR inhibition and also led to better memory potential. Being aware of the heterogeneity within CD8+ T
cell populations, and that aging leads to an increased…
Advisors/Committee Members: Oxenius, Annette, Jessberger, Sebastian, Barral, Yves.
Subjects/Keywords: T cell differentiation; T cell memory; asymmetric cell division
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CSE |
Export
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APA (6th Edition):
Borsa, M. (2018). Impact of asymmetric cell division on T cell differentiation. (Doctoral Dissertation). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/283722
Chicago Manual of Style (16th Edition):
Borsa, Mariana. “Impact of asymmetric cell division on T cell differentiation.” 2018. Doctoral Dissertation, ETH Zürich. Accessed February 26, 2020.
http://hdl.handle.net/20.500.11850/283722.
MLA Handbook (7th Edition):
Borsa, Mariana. “Impact of asymmetric cell division on T cell differentiation.” 2018. Web. 26 Feb 2020.
Vancouver:
Borsa M. Impact of asymmetric cell division on T cell differentiation. [Internet] [Doctoral dissertation]. ETH Zürich; 2018. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/20.500.11850/283722.
Council of Science Editors:
Borsa M. Impact of asymmetric cell division on T cell differentiation. [Doctoral Dissertation]. ETH Zürich; 2018. Available from: http://hdl.handle.net/20.500.11850/283722
University of Hong Kong
19.
陳思潁; Chan, Sze-wing, Scarlet.
Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies.
Degree: PhD, 2000, University of Hong Kong
URL: Chan,
S.
S.
[陳思潁].
(2000).
Erythroleukemic
cell
differentiation
factor
(EDF)
:
biochemical,
cloning,
molecular
structure,
and
functional
studies.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b3026907
;
http://dx.doi.org/10.5353/th_b3026907
;
http://hdl.handle.net/10722/31906
published_or_final_version
abstract
Anatomy
Doctoral
Doctor of Philosophy
Subjects/Keywords: Cell differentiation.; Erythrocytes.
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
陳思潁; Chan, Sze-wing, S. (2000). Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies. (Doctoral Dissertation). University of Hong Kong. Retrieved from Chan, S. S. [陳思潁]. (2000). Erythroleukemic cell differentiation factor (EDF) : biochemical, cloning, molecular structure, and functional studies. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b3026907 ; http://dx.doi.org/10.5353/th_b3026907 ; http://hdl.handle.net/10722/31906
Chicago Manual of Style (16th Edition):
陳思潁; Chan, Sze-wing, Scarlet. “Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies.” 2000. Doctoral Dissertation, University of Hong Kong. Accessed February 26, 2020.
Chan, S. S. [陳思潁]. (2000). Erythroleukemic cell differentiation factor (EDF) : biochemical, cloning, molecular structure, and functional studies. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b3026907 ; http://dx.doi.org/10.5353/th_b3026907 ; http://hdl.handle.net/10722/31906.
MLA Handbook (7th Edition):
陳思潁; Chan, Sze-wing, Scarlet. “Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies.” 2000. Web. 26 Feb 2020.
Vancouver:
陳思潁; Chan, Sze-wing S. Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies. [Internet] [Doctoral dissertation]. University of Hong Kong; 2000. [cited 2020 Feb 26].
Available from: Chan, S. S. [陳思潁]. (2000). Erythroleukemic cell differentiation factor (EDF) : biochemical, cloning, molecular structure, and functional studies. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b3026907 ; http://dx.doi.org/10.5353/th_b3026907 ; http://hdl.handle.net/10722/31906.
Council of Science Editors:
陳思潁; Chan, Sze-wing S. Erythroleukemic cell differentiation factor (EDF):
biochemical, cloning, molecular structure, and
functionalstudies. [Doctoral Dissertation]. University of Hong Kong; 2000. Available from: Chan, S. S. [陳思潁]. (2000). Erythroleukemic cell differentiation factor (EDF) : biochemical, cloning, molecular structure, and functional studies. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b3026907 ; http://dx.doi.org/10.5353/th_b3026907 ; http://hdl.handle.net/10722/31906
University of Hong Kong
20.
谭志佳; Tan, Zhijia.
Molecular analyses of chondrocyte differentiation and
adaptation to ER stress.
Degree: PhD, 2013, University of Hong Kong
URL: Tan,
Z.
[谭志佳].
(2013).
Molecular
analyses
of
chondrocyte
differentiation
and
adaptation
to
ER
stress.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b5016250
;
http://dx.doi.org/10.5353/th_b5016250
;
http://hdl.handle.net/10722/209435
► Endochondral bone development depends on the progression of chondrocyte proliferation, hypertrophy and terminal differentiation, which requires precise transcriptional regulation and signaling coordination. Disturbance of this…
(more)
▼ Endochondral bone development depends on the
progression of chondrocyte proliferation, hypertrophy and terminal
differentiation, which requires precise transcriptional regulation
and signaling coordination. Disturbance of this process would
disrupt chondrocyte
differentiation and lead to chondrodysplasias.
In cells, a highly conserved mechanism, ER stress signaling, has
been developed to sense the protein load and maintain the cellular
homeostasis. In humans, mutations in COL10A1 induce ER stress and
result in metaphyseal chondrodysplasia type Schmid (MCDS). Previous
analysis of a MCDS mouse model (13deltg mouse) had revealed a novel
mechanism of chondrocyte adaptation to ER stress. The hypertrophic
chondrocytes survive ER stress by reverting to a pre-hypertrophic
like state (Tsang et al., 2007). To dissect the underlying
mechanisms that coordinate chondrocyte survival, reverted
differentiation and adaptation to ER stress, different chondrocyte
populations in the wild type and 13del growth plates were
fractionated for global gene expression analyses.
The
genome-wide expression profiles of proliferating chondrocytes,
prehypertrophic chondrocytes, hypertrophic chondrocytes and
terminally differentiated chondrocytes in the wild type growth
plate provide molecular bases to understand the processes
underlying both physiological and pathological bone growth.
Systematic analyses of these transcriptomic data revealed the gene
expression patterns and correlation in the dynamics of endochondral
ossification. Genes associated with sterol metabolism and
cholesterol biosynthesis are enriched in the prehypertrophic
chondrocytes. Selected genes (Wwp2, Zbtb20, Ppa1 and Ptgis) that
may potentially contribute to endochondral ossification were
identified differentially expressed in the growth plate.
Bioinformatics approaches were applied to predict regulatory
networks in chondrocytes at different
differentiation stages,
implying the essential and dominant roles of Sox9 in coordination
of stage specific gene expression. We further confirmed that Sox9
directly regulates the transcription of Cyr61, Lmo4, Ppa1, Ptch1
and Trps1, suggesting that Sox9 integrates different steps of
chondrocyte
differentiation via regulation of its target genes and
partially crosstalk with IHH signaling pathway.
The information
on gene expression and regulation from physiological growth plate
provides important basis to understand the molecular defects of
chondrodysplasia. The hypertrophic zone in 13del growth plate was
fractionated into upper, middle and lower parts for microarray
profiling, corresponding for the onset of ER stress, onset of
reverted
differentiation and adaptation phase. Comparative
transcriptomics of wild type and 13del growth plates revealed genes
related to glucose, amino acid and lipid metabolisms are up
regulated in response to ER stress. Fgf21 was identified as a novel
ER stress inducible factor regulated by ATF4. Removal of Fgf21
results in increasing
cell apoptosis in 13del hypertrophic zone
without affecting the reverted…
Advisors/Committee Members: Cheah, KSE.
Subjects/Keywords: Cell differentiation; Endoplasmic reticulum; Cartilage cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
谭志佳; Tan, Z. (2013). Molecular analyses of chondrocyte differentiation and
adaptation to ER stress. (Doctoral Dissertation). University of Hong Kong. Retrieved from Tan, Z. [谭志佳]. (2013). Molecular analyses of chondrocyte differentiation and adaptation to ER stress. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016250 ; http://dx.doi.org/10.5353/th_b5016250 ; http://hdl.handle.net/10722/209435
Chicago Manual of Style (16th Edition):
谭志佳; Tan, Zhijia. “Molecular analyses of chondrocyte differentiation and
adaptation to ER stress.” 2013. Doctoral Dissertation, University of Hong Kong. Accessed February 26, 2020.
Tan, Z. [谭志佳]. (2013). Molecular analyses of chondrocyte differentiation and adaptation to ER stress. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016250 ; http://dx.doi.org/10.5353/th_b5016250 ; http://hdl.handle.net/10722/209435.
MLA Handbook (7th Edition):
谭志佳; Tan, Zhijia. “Molecular analyses of chondrocyte differentiation and
adaptation to ER stress.” 2013. Web. 26 Feb 2020.
Vancouver:
谭志佳; Tan Z. Molecular analyses of chondrocyte differentiation and
adaptation to ER stress. [Internet] [Doctoral dissertation]. University of Hong Kong; 2013. [cited 2020 Feb 26].
Available from: Tan, Z. [谭志佳]. (2013). Molecular analyses of chondrocyte differentiation and adaptation to ER stress. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016250 ; http://dx.doi.org/10.5353/th_b5016250 ; http://hdl.handle.net/10722/209435.
Council of Science Editors:
谭志佳; Tan Z. Molecular analyses of chondrocyte differentiation and
adaptation to ER stress. [Doctoral Dissertation]. University of Hong Kong; 2013. Available from: Tan, Z. [谭志佳]. (2013). Molecular analyses of chondrocyte differentiation and adaptation to ER stress. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5016250 ; http://dx.doi.org/10.5353/th_b5016250 ; http://hdl.handle.net/10722/209435
University of Hong Kong
21.
Stillitano, Alexia.
miR-34a : a key regulator of adipogenesis.
Degree: Master of Medical Sciences, 2014, University of Hong Kong
URL: Stillitano,
A..
(2014).
miR-34a
:
a
key
regulator
of
adipogenesis.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b5319019
;
http://dx.doi.org/10.5353/th_b5319019
;
http://hdl.handle.net/10722/206552
► Introduction Globesity, the worldwide obesity epidemic, represents a major threat and public health burden. An uncontrolled expansion of the adipose tissue followed by a chronic…
(more)
▼ Introduction Globesity, the worldwide obesity
epidemic, represents a major threat and public health burden. An
uncontrolled expansion of the adipose tissue followed by a chronic
low-grade inflammation leads to the dysfunction of the adipose
organ resulting in obesity and its associated metabolic
complications. Uncovering the mechanisms of adipogenesis, the
development of adipocytes, therefore strikes as a key strategy in
combating the disease. MicroRNAs (miRs), a class of small
non-coding RNAs, have emerged in recent years as crucial modulators
of diverse biological processes such as cell proliferation,
differentiation, and signal transduction emphasizing their large
potential as targets. Numerous miRs have been associated with the
adipose tissue and metabolism and their dysregulation has
repeatedly been linked to diseases including diabetes and obesity.
This study aimed to investigate the role of miR-34a, an
obesity-related miR, in the regulation of pre-adipocyte
differentiation.
Materials and Methods Mouse 3T3-L1
pre-adipocytes were employed as an in vitro system to study
adipogenesis. Oil Red O staining served to evaluate the degree of
adipogenesis and the over-expression of miR-34a in adipocytes was
achieved by a lentiviral system. MiR and messenger RNA (mRNA)
levels were analysed using TaqMan and SYBR Green-based quantitative
real time PCR (qPCR) respectively.
Results The expression of
miR-34a was substantially down-regulated upon treatment of
differentiation medium for two days and remained significantly low
during the differentiation period compared with undifferentiated
pre-adipocytes. Lentivirus-mediated over-expression of miR-34a
successfully up-regulated miR-34a. Higher levels of miR-34a in turn
mitigated adipogenesis as evidenced by blunted Oil Red O staining.
This observation was found to be in good agreement with the qPCR
analysis, which showed a down-regulation of several key adipogenic
markers.
Conclusion The down-regulation of miR-34a is required
during pre-adipocyte differentiation for the efficient proceedings
of the adipogenic programme. Further investigation is needed to
evaluate the potential therapeutic implication of miR-34a-based
treatment in managing obesity.
published_or_final_version
Medicine
Master
Master of Medical Sciences
Subjects/Keywords: Fat cells; Cell differentiation; Small interfering RNA
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Stillitano, A. (2014). miR-34a : a key regulator of adipogenesis. (Masters Thesis). University of Hong Kong. Retrieved from Stillitano, A.. (2014). miR-34a : a key regulator of adipogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5319019 ; http://dx.doi.org/10.5353/th_b5319019 ; http://hdl.handle.net/10722/206552
Chicago Manual of Style (16th Edition):
Stillitano, Alexia. “miR-34a : a key regulator of adipogenesis.” 2014. Masters Thesis, University of Hong Kong. Accessed February 26, 2020.
Stillitano, A.. (2014). miR-34a : a key regulator of adipogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5319019 ; http://dx.doi.org/10.5353/th_b5319019 ; http://hdl.handle.net/10722/206552.
MLA Handbook (7th Edition):
Stillitano, Alexia. “miR-34a : a key regulator of adipogenesis.” 2014. Web. 26 Feb 2020.
Vancouver:
Stillitano A. miR-34a : a key regulator of adipogenesis. [Internet] [Masters thesis]. University of Hong Kong; 2014. [cited 2020 Feb 26].
Available from: Stillitano, A.. (2014). miR-34a : a key regulator of adipogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5319019 ; http://dx.doi.org/10.5353/th_b5319019 ; http://hdl.handle.net/10722/206552.
Council of Science Editors:
Stillitano A. miR-34a : a key regulator of adipogenesis. [Masters Thesis]. University of Hong Kong; 2014. Available from: Stillitano, A.. (2014). miR-34a : a key regulator of adipogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5319019 ; http://dx.doi.org/10.5353/th_b5319019 ; http://hdl.handle.net/10722/206552
University of New Mexico
22.
Wilson, Melissa R.
ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE.
Degree: UNM Biology Department, 2014, University of New Mexico
URL: https://digitalrepository.unm.edu/biol_etds/114
► Yeast cells in stationary phase cultures, after several days growth in rich, glucose-based medium (YPD), are separable by density-gradient centrifugation into two fractions. The heavier,…
(more)
▼ Yeast cells in stationary phase cultures, after several days growth in rich, glucose-based medium (YPD), are separable by density-gradient centrifugation into two fractions. The heavier, quiescent cells are mostly virgin daughters whereas the less-dense, non-quiescent cells, are a typical mixture of daughters to aged cells. Quiescent cells can also be separated based on expression of specific GFP-tagged proteins, including many that are localized to the mitochodria. To ask the question, what genes are required for this
differentiation process, we used a combination of the diploid, homozygous yeast deletion set, the heterozygous deletion set (carrying one deleted 'essential' gene) and a third set designed to reduce mRNA abundance of a number of 'essential' genes. Samples from the cultures just prior to the diauxic shift (just prior to glucose exhaustion), stationary phase, and isolated quiescent (Q) and nonquiescent (NQ) cells were harvested and technical and biological replicates analyzed by microarray analysis. The results showed that deletions in more than 500 genes resulted in 2-fold or greater reduction in Q-
cell formation. Thus, almost 10% of genes in the yeast genome were important for Q-
cell formation. When mutants with a 2-fold in Q vs all other samples were compared, 411 genes were identified that were important for Q cells vs DS, NQ, and SP. These genes encoded proteins involved in mitochondrial function, protein localization, and vesicle transport. We concluded from these results that
differentiation of quiescent cells requires a major cellular commitment and that the major functions required are similar to those identified by proteomic and transcriptomic analysis of Q cells done previously in our laboratory, furthering understanding of
cell differentiation.
Advisors/Committee Members: Werner-Washburne, Maggie, Natvig, Don, Northup, Diana.
Subjects/Keywords: yeast; Saccharomyces cerevisiae; quiescence; cell differentiation
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APA (6th Edition):
Wilson, M. R. (2014). ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE. (Masters Thesis). University of New Mexico. Retrieved from https://digitalrepository.unm.edu/biol_etds/114
Chicago Manual of Style (16th Edition):
Wilson, Melissa R. “ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE.” 2014. Masters Thesis, University of New Mexico. Accessed February 26, 2020.
https://digitalrepository.unm.edu/biol_etds/114.
MLA Handbook (7th Edition):
Wilson, Melissa R. “ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE.” 2014. Web. 26 Feb 2020.
Vancouver:
Wilson MR. ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE. [Internet] [Masters thesis]. University of New Mexico; 2014. [cited 2020 Feb 26].
Available from: https://digitalrepository.unm.edu/biol_etds/114.
Council of Science Editors:
Wilson MR. ANALYSIS OF GENES REQUIRED FOR QUIESCENT CELL FORMATION IN STATIONARY PHASE CULTURES OF SACCHAROMYCES CEREVISIAE. [Masters Thesis]. University of New Mexico; 2014. Available from: https://digitalrepository.unm.edu/biol_etds/114
University of Rochester
23.
Llamas, Fernando Ontiveros.
The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses.
Degree: PhD, 2010, University of Rochester
URL: http://hdl.handle.net/1802/9819
► CD4+ T cells play multiple roles within the adaptive immune system. One of these roles concerns the qualitative and quantitative modification of the CD8+ T…
(more)
▼ CD4+ T cells play multiple roles within the
adaptive immune system. One of these
roles concerns the
qualitative and quantitative modification of the CD8+ T cell
response, a phenomenon termed CD4 help. Although primary CD8
responses against
pathogens are largely independent of the
presence of CD4+ T cells, responses directed
to cell-associated
antigens show variable dependence on CD4 help. This variability is
likely a result of the different degrees of activation of the
innate immune system
inherent in diverse models of immunization.
Our laboratory has developed a
Dendritic Cell-based model of
immunization that shows a strong dependency on CD4
help. We used
this model and a traditional crosspriming system to test the
hypothesis
that in pathogen-free systems, either inflammation or
activation of NK cells would be
instrumental in the generation of
primary CD8 responses in the absence of CD4 help.
Such immune
responses could prove detrimental if resulting in unchecked
expansion
of self-reactive CD8 T cells or beneficial in
immunocompromised individuals with
deficient CD8 responses due to
the lack of a functional CD4+ compartment. We
found that neither
NK cell activation nor exposure to the inflammatory cytokine
TNF!
was sufficient to bypass the requirement for CD4 help. However, a
different
kind of signal, IFN!, proved to be enough to rescue CD8
responses in CD4-depleted
mice. Our results are in line with
previous findings on the effects of IFN! on CD8
responses. The
effects of inflammatory signals on CD4 differentiation were also
tested. Primed CD4+ T cells acquire distinct effector phenotypes,
among them Th1
and Th2. A more recently described phenotype is
characterized by the secretion of ILvi
2 and numerous chemokines,
the expression of CD73 and the ability to further
differentiate
into distinct committed phenotypes. To this date, the in vitro
differentiation of this cell subset has remained dependent on
culture conditions that
also induce the expression of Foxp3+
regulatory T cells. Preliminary data in our
laboratory suggested
that the combination of IL-6 and TGF" induced the
differentiation
of IL-2 secreting cells while preventing the generation of
regulatory T
cells. We formally tested the ability of these
cytokines to induce the differentiation of
primed uncommitted CD4
cells. Cells primed by alloantigens under these conditions
expressed CD73 on their surface and differentiated into three main
groups: IL-4
producers, IL-17 producers and IL-2 producers. After
single cell sorting and cloning,
we found that the IL-2 producing
subset showed similar “commitment” flexibility to
that shown by
the previously described primed uncommitted cells.
Subjects/Keywords: CD4 Help; CD4 Differentiation; Dendritic Cell; Inflammation
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MLA ·
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CSE |
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APA (6th Edition):
Llamas, F. O. (2010). The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/9819
Chicago Manual of Style (16th Edition):
Llamas, Fernando Ontiveros. “The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses.” 2010. Doctoral Dissertation, University of Rochester. Accessed February 26, 2020.
http://hdl.handle.net/1802/9819.
MLA Handbook (7th Edition):
Llamas, Fernando Ontiveros. “The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses.” 2010. Web. 26 Feb 2020.
Vancouver:
Llamas FO. The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses. [Internet] [Doctoral dissertation]. University of Rochester; 2010. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1802/9819.
Council of Science Editors:
Llamas FO. The Influence of Innate Immune Mechanisms on CD4+ and
CD8+ T Cell Responses. [Doctoral Dissertation]. University of Rochester; 2010. Available from: http://hdl.handle.net/1802/9819
University of Kansas
24.
Newton, Amy Nicole.
Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation.
Degree: PhD, Molecular Biosciences, 2014, University of Kansas
URL: http://hdl.handle.net/1808/19603
► The differentiation of multipotent naïve T cells is influenced by the microenvironment. Cytokines, costimulatory proteins and other biological factors can tune this differentiation process, influencing…
(more)
▼ The
differentiation of multipotent naïve T cells is influenced by the microenvironment. Cytokines, costimulatory proteins and other biological factors can tune this
differentiation process, influencing
cell fate. Controlling naïve T
cell differentiation can guide the type of immune response elicited since each T
cell subset has a specific function in the immune system. In this dissertation, I examine the participation of costimulatory molecules expressed on the surface of naïve CD4+ T cells in
differentiation of these cells. I demonstrate that stimulation through the TCR and CTLA-4 directs naïve CD4+ T
cell differentiation to regulatory T cells in the absence of exogenous cytokines. I evaluate how combined stimuli influence
differentiation and function in T cells. Combined stimulation through CTLA-4 and CD28 (CD3+CD28+CTLA-4) results in distinct functional outcomes from combined stimulation through CTLA-4 and ICAM-1 (CD3+ICAM-1+CTLA-4) or alternatively, ICAM-1 and CD28 (CD3+CD28+ICAM-1).
Differentiation to Th1, Th2 or Treg cells has been evaluated in our previous studies. In this dissertation, I extend these studies by examining whether costimulation in the absence of exogenous cytokines can support Th17
differentiation. I found that costimulation through ICAM-1, CD28, LFA-1, or CTLA-4 did not activate naïve CD4+ T cells to differentiate to Th17 cells. I also evaluated how the low affinity IgE receptor, CD23, expressed on T cells participates in naïve T
cell differentiation and mature T
cell function. CD23 functions as a negative regulator of Th2 responses by inhibiting
differentiation of naïve T cells to Th2 cells and enhancing activation of Th1 cells in mature T cells. Next, I examined how lipoproteins relevant to atherosclerosis may guide
differentiation of naïve CD4+ T cells. Consistent with their known roles in promoting or inhibiting atherosclerosis, oxLDL activates
differentiation to Th1 cells whereas HDL inhibits T
cell proliferation and viability. Different responses by naïve T cells to these lipoproteins may have direct implications in how atherosclerosis is exacerbated or attenuated during disease. Finally, I explore whether autoimmunity is involved in a mouse model of emphysema. I demonstrate that T cells adoptively transferred emphysema to naïve, immunodeficient mice, supporting a role for autoimmunity in an elastase-induced model. Peptide therapy targeting the interactions between ICAM-1 and LFA-1 was able to reduce severity of emphysema as well.
Advisors/Committee Members: Benedict, Stephen H (advisor), Yankee, Thomas (cmtemember), Egan, Susan (cmtemember), Hefty, Scott (cmtemember), Davido, David (cmtemember).
Subjects/Keywords: Immunology; CTLA-4; differentiation; T cell
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APA ·
Chicago ·
MLA ·
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CSE |
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Manager
APA (6th Edition):
Newton, A. N. (2014). Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/19603
Chicago Manual of Style (16th Edition):
Newton, Amy Nicole. “Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation.” 2014. Doctoral Dissertation, University of Kansas. Accessed February 26, 2020.
http://hdl.handle.net/1808/19603.
MLA Handbook (7th Edition):
Newton, Amy Nicole. “Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation.” 2014. Web. 26 Feb 2020.
Vancouver:
Newton AN. Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation. [Internet] [Doctoral dissertation]. University of Kansas; 2014. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1808/19603.
Council of Science Editors:
Newton AN. Novel roles for CD23, CTLA-4 and lipoproteins in human T cell function and differentiation. [Doctoral Dissertation]. University of Kansas; 2014. Available from: http://hdl.handle.net/1808/19603
The Ohio State University
25.
Hu, Rong.
Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS.
Degree: PhD, Molecular, Cellular, and Developmental
Biology, 2007, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1166644761
► The microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor, regulates distinct target genes in several cell types including osteoclasts. Osteoclasts are…
(more)
▼ The microphthalmia-associated transcription factor
(MITF), a basic helix-loop-helix leucine zipper (bHLH-Zip)
transcription factor, regulates distinct target genes in several
cell types including osteoclasts. Osteoclasts are terminally
differentiated multinuclear cells responsible for bone resorption.
CSF-1 and RANKL are two critical cytokines to induce osteoclast
differentiation from bone morrow-derived precursors. In
osteoclasts, MITF interacts with the Ets family transcription
factor PU.1 to synergistically activate target genes like Cathepsin
K (Ctsk) and Acid Phosphatase 5 (Acp5). The region of MITF required
for the physical interaction with PU.1 is the bHLH-Zip domain. To
finer map the interacting domain of MITF, we introduced point
mutations into the loop region of MITF via in vitro site-directed
mutagenesis. The properties of mutated MITF proteins were analyzed
by transient transfection assays, EMSAs, and in vitro GST pulldown
assays. We identified that specific amino acids including N235,
D236, and W241 in the loop region of MITF are critical to mediate
physical and functional interaction with PU.1. Both MITF and PU.1
are known transcriptional activators in osteoclasts. Results
presented here demonstrate that they can also act as components of
repressor complexes that suppress target gene expression in
committed myeloid precursors. The direct interaction of MITF and
PU.1 with the zinc-finger protein Eos, an Ikaros family member,
appears to be necessary for repression of Ctsk and Acp5. In bone
marrow-derived precursors treated with CSF-1 alone, Eos formed a
complex with MITF and PU.1 at target gene promoters and suppressed
transcription through recruitment of co-repressors CtBP and Sin3A.
Eos expression was reduced during osteoclast
differentiation
initiated by combined CSF-1 and RANKL stimulation and Eos
association with Ctsk and Acp5 promoters was significantly
decreased. Subsequently, MITF and PU.1 recruited co-activators to
these target promoters resulting in robust expression of target
genes. Overexpression of Eos in bone marrow-derived precursors
inhibited multinuclear osteoclast formation and repressed
transcription of subset of osteoclast specific genes that are
regulated by MITF and PU.1. This work provides a novel mechanism to
account for the modulation of MITF and PU.1 activity in committed
myeloid progenitors prior to the initiation of osteoclast
differentiation in response to the appropriate extracellular
signals.
Advisors/Committee Members: Ostrowski, Michael (Advisor).
Subjects/Keywords: Biology, Molecular; Cell differentiation; osteoclasts; transcriptional regulation
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hu, R. (2007). Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1166644761
Chicago Manual of Style (16th Edition):
Hu, Rong. “Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS.” 2007. Doctoral Dissertation, The Ohio State University. Accessed February 26, 2020.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1166644761.
MLA Handbook (7th Edition):
Hu, Rong. “Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS.” 2007. Web. 26 Feb 2020.
Vancouver:
Hu R. Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS. [Internet] [Doctoral dissertation]. The Ohio State University; 2007. [cited 2020 Feb 26].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1166644761.
Council of Science Editors:
Hu R. Regulation of osteoclast differentiation by transcription
factors MITF, PU.1 and EOS. [Doctoral Dissertation]. The Ohio State University; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1166644761
Ohio University
26.
Wang, Han.
The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation.
Degree: PhD, Chemistry and Biochemistry (Arts and
Sciences), 2013, Ohio University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1363779566
► Human embryonic stem cells (hESCs) have the potential to grow into almost all types of cells in the human body. This special property makes hESC…
(more)
▼ Human embryonic stem cells (hESCs) have the potential
to grow into almost all types of cells in the human body. This
special property makes hESC invaluable for the restoration of
tissue function after damage from different diseases like
Parkinson's disease, Alzheimer’s disease, stroke, and diabetes. The
potential therapeutic applications of hESC have been hindered by a
lack of knowledge of the
differentiation mechanisms. It is not
clear what kind of message has to be delivered to hESC to start
differentiation, and what process leads to the selected
cell
differentiation directions. At this stage of research, it is
impossible to direct the
differentiation of hESC to functional
specific cells for the restoration of damaged tissues. This study
focused on the role of small, diffusible molecules on hESC
differentiation. We hypothesized that nitric oxide (NO) and/or
peroxynitrite (ONOO-) may play a role as redox mediators during
early embryogenesis. After having working
cell banks of mouse
fibroblasts and hESCs, an eighteen-day hESC early
differentiation
system was established through the formation of embryoid bodies
(EBs). The
differentiation status of cells was evaluated through
flow cytometry, proteome profiler arrays, and immunocytostaining. A
nanomedical approach was used in this study. The bioavailable NO
and ONOO- concentration was measured with selective electrochemical
nanosensors during the
differentiation process. A detailed profile
of the NO and ONOO- concentrations as a function of time during the
differentiation process was established. Also, several compounds
which can influence the NO or ONOO- production were used to treat
the cells during the
differentiation process. We found that in the
established
differentiation system, the
differentiation of hESC
towards all three germ layers occurred. NO and ONOO- were both
available in the microenvironment during hESC
differentiation. We
proved that both NO and ONOO- were crucial to the
differentiation
process and had a facilitating effect on the production of
neuroectoderm cells. NO has a profound inhibitory effect on the
production of mesoderm cells. This study is the first to
demonstrate on the molecular level that both NO and ONOO- play a
fundamental redox regulatory role in the early
differentiation of
hESCs.
Advisors/Committee Members: Malinski, Tadeusz (Committee Chair).
Subjects/Keywords: Biochemistry; Nitric Oxide; Stem Cell; Peroxynitrite; Differentiation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, H. (2013). The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation. (Doctoral Dissertation). Ohio University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1363779566
Chicago Manual of Style (16th Edition):
Wang, Han. “The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation.” 2013. Doctoral Dissertation, Ohio University. Accessed February 26, 2020.
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1363779566.
MLA Handbook (7th Edition):
Wang, Han. “The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation.” 2013. Web. 26 Feb 2020.
Vancouver:
Wang H. The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation. [Internet] [Doctoral dissertation]. Ohio University; 2013. [cited 2020 Feb 26].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1363779566.
Council of Science Editors:
Wang H. The Role of Nitric Oxide and Peroxynitrite in Human
Embryonic Stem Cell Differentiation. [Doctoral Dissertation]. Ohio University; 2013. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1363779566
University of Western Australia
27.
Thomas, Elizabeth.
Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium.
Degree: PhD, 2012, University of Western Australia
URL: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=34751&local_base=GEN01-INS01
► [Truncated abstract] Several lines of evidence for the self-‐renewal capacity and multi-‐lineage potential (hallmark properties of stem cells) of Primary Mammary Epithelial Cells (PMEC) from…
(more)
▼ [Truncated abstract] Several lines of evidence for the self-‐renewal capacity and multi-‐lineage potential (hallmark properties of stem cells) of Primary Mammary Epithelial Cells (PMEC) from the human lactating gland are presented in this thesis. These cells are explored with respect to multiple signaling pathways that may be involved in regulation of this novel phenotype. We demonstrate a difference between PMEC derived from the lactating breast compared to the non-‐lactating breast, and propose that this phenotype may represent a putative human committed progenitor cell (CPC), and be important in normal secretory differentiation. We further speculate that this cell may possess properties that underlie a distinct set of breast cancers, consistent with mouse models. This is outlined in each of the three publications that comprise this thesis. In Publication 1 (P1) we demonstrated that epithelial cells isolated and purified from human breastmilk express the transcription factor p63, a known marker of mammary epithelial or 'basal' cells, that promotes transcription of pro-‐ mitotic genes. Upon differentiation p63 expression is lost and adherent cells begin to express 14-‐3-‐3sigma (14-‐3-‐3σ), a known negative regulator of cell-‐ cycle proteins in differentiating epithelium. At the end of cell number expansion, adherent cells down-‐regulate 14-‐3-‐3σ and distinct subpopulations begin to express markers of the differentiated lactating gland including CK18 (luminal cells) and CK14 (myoepithelial cells).
This is direct evidence that p63+ cells from Breastmilk posses multilineage differentiation capacity, a hallmark of stem cells. By forced down-‐regulation of 14-‐3-‐3σ we were able to increase the cell-‐doubling capacity of the p63+ cells without effecting the pattern of differentiation and distribution of resulting differentiated phenotypes. More recently, regulation of 14-‐3-‐3σ expression has been shown to be mediated by micro-‐RNA-‐directed methylation of the 14-‐3-‐3σ promoter, providing a mechanism to inhibit cell-‐cycle arrest and promote proliferation in mammary epithelial cells. It is still not clear if or how p63 may be involved in this process. In Publication 2 (P2)we further investigated the Primary Mammary Epithelial Cells (PMEC) from lactating tissue and demonstrated that the p63+ cells also express the mammary stem cell marker CD49f, which supports our proposal that these cells may be multipotent stem cells from the mammary epithelium. We also demonstrated that in non-‐differentiating growth media these cells maintain a higher proportion of self-‐renewing cells in extracellular matrix (ECM). In ECM culture, the PMEC are capable of forming a completely differentiated alveolar structure composed of a basal layer of CD49f+ cells and a luminal layer of CK18+ cells. The PMEC show unique response to the Pregnancy-‐associated Hormones (PAH) Prolactin (PL), Placental Lactogen (PL) and RANKL compared to Human Mammary Epithelial Cells HMEC derived from non-‐lactating tissue and mammary cell lines, and response to…
Subjects/Keywords: Mammary gland; Stem cell; Differentiation; Breast cancer
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APA ·
Chicago ·
MLA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thomas, E. (2012). Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium. (Doctoral Dissertation). University of Western Australia. Retrieved from http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=34751&local_base=GEN01-INS01
Chicago Manual of Style (16th Edition):
Thomas, Elizabeth. “Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium.” 2012. Doctoral Dissertation, University of Western Australia. Accessed February 26, 2020.
http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=34751&local_base=GEN01-INS01.
MLA Handbook (7th Edition):
Thomas, Elizabeth. “Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium.” 2012. Web. 26 Feb 2020.
Vancouver:
Thomas E. Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium. [Internet] [Doctoral dissertation]. University of Western Australia; 2012. [cited 2020 Feb 26].
Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=34751&local_base=GEN01-INS01.
Council of Science Editors:
Thomas E. Tissue-specific stem cells in mammary epithelial differentiation : identification of a putative human committed progenitor cell unique to lactating epithelium. [Doctoral Dissertation]. University of Western Australia; 2012. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=34751&local_base=GEN01-INS01
Louisiana State University
28.
Flanagan, Michael B.
Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells.
Degree: PhD, Medicine and Health Sciences, 2013, Louisiana State University
URL: etd-11182013-150645
;
https://digitalcommons.lsu.edu/gradschool_dissertations/3709
► Stem cells exist in various tissues, including dental follicles and dental pulps. Adult stem cells (ASC) can be isolated from patients for autologous transplantation, which…
(more)
▼ Stem cells exist in various tissues, including dental follicles and dental pulps. Adult stem cells (ASC) can be isolated from patients for autologous transplantation, which eliminates the risk of immune rejection with low or no tumorigenesis. However, one of the challenges is that ASC progressively lose their differentiation ability when cultured in vitro. This prevents expansion of large quantities of high-potential stem cells for therapeutics, especially for stem cells with limited tissue source, such as dental pulp stem cells (DPSC). The goal of this study is to define possible molecular regulation causing loss of differentiation. To achieve this goal, we determined that DPSC at passages 3 and 5 (early passage) possessed strong differentiation capability, and such differentiation capability is completely lost at passage 11 (late passage). Using whole-genome microarray to compare the transcriptomes, we found that the expression of 34 genes were decreased for more than 10-fold in p11 DPSC when compared to p3. After confirming gene expression with RT-PCR, heat shock protein B8 (HspB8) and the GIPC PDZ domain-containing family (Gipc2) were selected for siRNA knockdown study. Knockdown of HspB8 in early-passage DPSC resulted in the cells losing differentiation, but knockdown of Gipc2 had no effect, suggesting that HspB8 plays an important role in maintaining DPSC differentiation. To further study HspB8, we constructed 2 vectors, one containing the coding sequence (CDS) and 3’ untranslated region (3’UTR) and another containing only the CDS. Transfection of the vectors into early passage DPSC dramatically increased both HspB8 mRNA and protein. However, transfection of the vectors into the late passage DPSC resulted in overexpression of HspB8 mRNA, but increase of HspB8 protein was seen only in CDS transfection. Given that 3’UTR of mRNA is the major target region for microRNAs (miRNAs), the results indicate that miRNAs are responsible for down-regulation of HspB8 in long-term culture of DPSCs. We conclude that high-level HspB8 expression is essential for differentiation of DPSC, and down-regulation of HspB8 in cultured DPSC is likely due to increased expression of miRNAs. These are novel findings regarding HspB8 and miRNAs on the regulation of stem cell fate.
Subjects/Keywords: dental pulp; adult stem cell; DPSC; differentiation
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APA (6th Edition):
Flanagan, M. B. (2013). Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-11182013-150645 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3709
Chicago Manual of Style (16th Edition):
Flanagan, Michael B. “Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells.” 2013. Doctoral Dissertation, Louisiana State University. Accessed February 26, 2020.
etd-11182013-150645 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3709.
MLA Handbook (7th Edition):
Flanagan, Michael B. “Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells.” 2013. Web. 26 Feb 2020.
Vancouver:
Flanagan MB. Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells. [Internet] [Doctoral dissertation]. Louisiana State University; 2013. [cited 2020 Feb 26].
Available from: etd-11182013-150645 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3709.
Council of Science Editors:
Flanagan MB. Identification of genes responsible for maintenance of differentiation capability in dental pulp stem cells. [Doctoral Dissertation]. Louisiana State University; 2013. Available from: etd-11182013-150645 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3709
University of Saskatchewan
29.
Bingham, Erin Jennifer.
A metabolomic investigation of key cellular processes relating to cancer development and progression.
Degree: 2010, University of Saskatchewan
URL: http://hdl.handle.net/10388/etd-09222010-141919
► Recent advancements in mass spectrometry have facilitated new analytical approaches capable of comprehensively characterizing metabolites in biological samples. Fourier transform ion cyclotron resonance mass spectrometry…
(more)
▼ Recent advancements in mass spectrometry have facilitated new analytical approaches capable of comprehensively characterizing metabolites in biological samples. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) combines excellent mass accuracy (ppm
Advisors/Committee Members: Warrington, Robert, Ritchie, Shawn, Moore, Stan, Hatch, Grant, Khandelwal, Ramji, Mousseau, Darrell, Pato, Mary.
Subjects/Keywords: Transformation; Cell cycle; Differentiation; Metabolomics; Lipids; Cancer
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APA (6th Edition):
Bingham, E. J. (2010). A metabolomic investigation of key cellular processes relating to cancer development and progression. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/etd-09222010-141919
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):
Bingham, Erin Jennifer. “A metabolomic investigation of key cellular processes relating to cancer development and progression.” 2010. Thesis, University of Saskatchewan. Accessed February 26, 2020.
http://hdl.handle.net/10388/etd-09222010-141919.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bingham, Erin Jennifer. “A metabolomic investigation of key cellular processes relating to cancer development and progression.” 2010. Web. 26 Feb 2020.
Vancouver:
Bingham EJ. A metabolomic investigation of key cellular processes relating to cancer development and progression. [Internet] [Thesis]. University of Saskatchewan; 2010. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/10388/etd-09222010-141919.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bingham EJ. A metabolomic investigation of key cellular processes relating to cancer development and progression. [Thesis]. University of Saskatchewan; 2010. Available from: http://hdl.handle.net/10388/etd-09222010-141919
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
30.
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa, Hiromasa.
Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化.
Degree: 博士（歯学）, 2014, Matsumoto Dental University / 松本歯科大学
URL: http://id.nii.ac.jp/1070/00002235/
► The expression of HSP27 and some CKs were examined the 40 cases of typical solid/multicystic ameloblastoma using immunohistochemical techniques. In order to examine the relevance…
(more)
▼ The expression of HSP27 and some CKs were examined the 40 cases of typical solid/multicystic ameloblastoma using immunohistochemical techniques. In order to examine the relevance of HSP in cell differentiation, we focused on the cytoskeletal expression of CK. CK19 is a marker of typical odontogenic epithelium widely observed in follicular and plexiform types of ameloblastomas. Since staining with CK14 is one of the measures of the differentiation potential of squamous cells and is extensively expressed in both follicular and plexiform types, it implies that squamous differentiation of each type can occur. CK8 was strongly detected in tumor nests in plexiform type but weakly detected in follicular type. It was considered that the expression of HSP27 in plexiform type correlated with the expression of CK8 suggesting that HSP27 might have regulated the expression of CK8.
2013
Subjects/Keywords: ameloblatoma; immunohistochemistry; HSP; CK; cell differentiation; immunohistochemistry
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APA ·
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MLA ·
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CSE |
Export
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APA (6th Edition):
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa, H. (2014). Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化. (Thesis). Matsumoto Dental University / 松本歯科大学. Retrieved from http://id.nii.ac.jp/1070/00002235/
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):
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa, Hiromasa. “Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化.” 2014. Thesis, Matsumoto Dental University / 松本歯科大学. Accessed February 26, 2020.
http://id.nii.ac.jp/1070/00002235/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa, Hiromasa. “Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化.” 2014. Web. 26 Feb 2020.
Vancouver:
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa H. Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化. [Internet] [Thesis]. Matsumoto Dental University / 松本歯科大学; 2014. [cited 2020 Feb 26].
Available from: http://id.nii.ac.jp/1070/00002235/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fujita, Muneteru; Nakano, Keisuke; Funato, Akiyoshi; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Okafuji, Norimasa; Hasegawa H. Heat Shock Protein27 Expression and Cell Differentiation in Ameloblastomas : エナメル上皮腫におけるHeat Shock Protein27の発現と細胞分化. [Thesis]. Matsumoto Dental University / 松本歯科大学; 2014. Available from: http://id.nii.ac.jp/1070/00002235/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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Open Access Theses and Dissertations