subject:(embryonic stem cells)

1. Dingle, Yu-Ting Liu. In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies.

Degree: PhD, Biomedical Engineering, 2015, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:419530/

► Cell-based therapy is a promising treatment option for central nervous system (CNS) disease and injury, but therapy strategies require optimization to achieve clinical improvement. The… (more)

▼ Cell-based therapy is a promising treatment option for central nervous system (CNS) disease and injury, but therapy strategies require optimization to achieve clinical improvement. The primary motivation of this thesis is to gain knowledge of in vitro neuronal differentiation of stem cells and to develop three-dimensional (3D) culture models to investigate stem cell transplantation to the CNS. The first study in this thesis addressed the heterogeneity of mouse embryonic stem cell-derived dopamine neurons. In vitro, the percentage of calbindin+ subtype of DA neurons was higher than the calretinin+ subtype, which was a similar trend to in vivo. In addition, dopamine neuron subtype generation in vitro was not governed by exogenous sonic hedgehog and fibroblast growth factor 8. In the second study, we developed a scaffold-free, 3D neural spheroid culture using primary rat cerebral cortex cells. Cortical cells in agarose hydrogels containing round-bottom microwells self-assembled into spheroids. The 3D neural spheroids recapitulated key in vivo-like features including 3D neuronal and astroglial network formation, extracellular matrix production, electrical activity, circuitry formation via excitatory and inhibitory synapses, and brain-like mechanical properties. These physiologically relevant characteristics make these spheroids an effective in vitro model for the CNS. In the third study, we expanded the 3D culture technique to develop an in vitro model for stem cell transplantation to the CNS. To represent the host CNS tissue in vitro, trampoline-shaped 3D microtissues were fabricated using cortical cells. Neural stem cells (NSCs) in the form of spheroids were placed in the center of the CNS host trampoline microtissues, and NSC behavior in this transplantation model construct was monitored. In a proof-of-concept experiment, we utilized this model to test the effect of fibroblast growth factor 2 on NSC migration. Based on the microtissue characterization results, this 3D in vitro transplantation model has the potential to generate more translatable results than 2D co-culture platforms. These works together contribute to a deeper understanding of in vitro generation of neurons and provide a novel in vitro 3D engineered CNS model for the investigation of cell-based therapies. Advisors/Committee Members: Hoffman-Kim, Diane (Director), Morgan, Jeffrey (Reader), Darling, Eric (Reader), Coulombe, Kareen (Reader), Kaplan, David (Reader).

Subjects/Keywords: mouse embryonic stem cells

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APA (6^th Edition):

Dingle, Y. L. (2015). In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419530/

Chicago Manual of Style (16^th Edition):

Dingle, Yu-Ting Liu. “In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies.” 2015. Doctoral Dissertation, Brown University. Accessed March 06, 2021. https://repository.library.brown.edu/studio/item/bdr:419530/.

MLA Handbook (7^th Edition):

Dingle, Yu-Ting Liu. “In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies.” 2015. Web. 06 Mar 2021.

Vancouver:

Dingle YL. In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Mar 06]. Available from: https://repository.library.brown.edu/studio/item/bdr:419530/.

Council of Science Editors:

Dingle YL. In Vitro Modeling of the Central Nervous System: Towards Optimized Cell-based Therapies. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419530/

University of Cambridge

2. Hodgson, Andrew Christopher. Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells.

Degree: PhD, 2017, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/267893

► This thesis presents the development of microfluidic devices designed to facilitate research into mouse embryonic stem cells (ESCs). ESCs are a well-studied cell, largely due… (more)

▼ This thesis presents the development of microfluidic devices designed to facilitate research into mouse embryonic stem cells (ESCs). ESCs are a well-studied cell, largely due to their pluripotent nature, meaning they are able to differentiate into all cell types of the body and may self-renew indefinitely in appropriate culture conditions. ESCs, along with many other lines of biological enquiry, are increasingly studied with the use of micro uidic technology which enables fine tuning of physical and chemical environments unachievable on the macro scale. Two varieties of microfluidic technology are presented in this thesis, one for high- resolution mechanical phenotyping of ESCs and the second as a novel in-chip culturing platform to study cellular transitions. Chapter 1 presents a broad introduction to ESCs and biological enquiry with microfluidics, aimed to underpin the following Chapters. Chapters 2 and 3 present self-contained projects, thus each include a motivation and introduction section more specific than that presented in Chapter 1. These Chapters also contain their own methods, results and conclusion sections. Finally, Chapter 4 presents a summary of the work performed along with an outlook of upcoming investigations. In Chapter 2, I present a microfluidic device developed and utilised in collaboration with Christophe Verstreken (Department of Physics, University of Cambridge), which has been used to apply a mechanical stress to live cells enabling measurement of their nuclear deformability. The device facilitates detection of both nucleus and cytoplasm which can then be analysed with a custom-written MATLAB code. Quantitative measurements of nuclear sizes and strains of ESCs indicated a negative Poisson ratio for nuclei of cells cultured in specific medium conditions. Furthermore, we demonstrate that the device can be used to physically phenotype at high-throughput by detecting changes in the nuclear response after treatment with actin depolymerising and chromatin decondensing agents. Finally, we show the device can be used for biologically relevant high-resolution confocal imaging of cells under compression. The work from this chapter is presented in Hodgson et al. [1]. In Chapter 3, I present a novel microfluidic platform developed in collaboration with Prof. Austin Smith and Dr Carla Mulas (Centre for Stem Cell Research, Cambridge). The developed platform enables individual ESCs to be cultured under continued observation as they exit their pluripotent stem cell state. Each cell within the device may be extracted from the chip at any time for further investigation without disturbing other cells. Assessing the transition from the stem cell state in individual cells is paramount if we are to understand the mechanisms of pluripotency.

Subjects/Keywords: Microfluidics; Embryonic Stem Cells; Pluripotency

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APA (6^th Edition):

Hodgson, A. C. (2017). Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/267893

Chicago Manual of Style (16^th Edition):

Hodgson, Andrew Christopher. “Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells.” 2017. Doctoral Dissertation, University of Cambridge. Accessed March 06, 2021. https://www.repository.cam.ac.uk/handle/1810/267893.

MLA Handbook (7^th Edition):

Hodgson, Andrew Christopher. “Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells.” 2017. Web. 06 Mar 2021.

Vancouver:

Hodgson AC. Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2017. [cited 2021 Mar 06]. Available from: https://www.repository.cam.ac.uk/handle/1810/267893.

Council of Science Editors:

Hodgson AC. Microfluidic Devices for the Investigation of Pluripotency in Embryonic Stem Cells. [Doctoral Dissertation]. University of Cambridge; 2017. Available from: https://www.repository.cam.ac.uk/handle/1810/267893

Central Connecticut State University

3. 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)

Subjects/Keywords: Cell differentiation; Embryonic stem cells

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APA (6^th 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 (16^th 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 March 06, 2021. 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 (7^th Edition):

Banda, Erin. “Identification of the first differentiation event involved in human embryonic stem cell-derived neural lineage specification.” 2010. Web. 06 Mar 2021.

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 2021 Mar 06]. 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 Bath

4. Kumpfmueller, Benjamin. Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4.

Degree: PhD, 2011, University of Bath

URL: https://researchportal.bath.ac.uk/en/studentthesis/control-of-embryonic-stem-cell-fate-the-role-of-phosphoinositide-3kinase-signalling-and-zscan4(439c6c52-1c06-4297-bd54-a97102875722).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550614

► Embryonic stem (ES) cells have the remarkable ability to differentiate into all cells comprising the three germ layers of the developing embryo. It is this… (more)

▼ Embryonic stem (ES) cells have the remarkable ability to differentiate into all cells comprising the three germ layers of the developing embryo. It is this pluripotency that makes them attractive for use in regenerative medicine. However, in order to harness this potential, we must understand the molecular mechanisms regulating the ability of ES cells to self-renew and thereby generate identical pluripotent daughter ES cells. The Welham laboratory has previously described a requirement for PI3K signalling in maintaining self-renewal of murine ES (mES) (Paling et al., 2004; Storm et al., 2007). To identify the molecular mechanisms involved in regulating mES cell self-renewal downstream of PI3K signalling, an Affymetrix microarray screen was carried out prior to the start of this PhD. For the screen, mES cells were grown in the presence of LIF and treated with the reversible PI3K inhibitor LY294002 (LY) or a DMSO control for 24, 48 and 72 hours. A total of 646 statistically significant transcriptional changes were detected and subsequently divided into 12 clusters using k-means clustering. Experiments using pharmacological inhibitors suggest that genes within the same cluster are regulated by common mechanisms. To identify potential candidates involved in regulation of mES cell pluripotency, further analyses concentrated on transcription factors and genes with unknown functions. In our microarray data Zscan4c, a member of a SCAN-domain containing Zinc finger protein family, is one of the earliest down-regulated probe-sets. Loss-of-function experiments using siRNA approaches highlight a role for Zscan4 downstream of PI3Ks in regulation of ES cell self-renewal. Immunohistochemical staining of cells overexpressing Zscan4c showed nuclear accumulation of the protein. This, together with the fact that Zscan4c was mainly detectable in the nuclear protein fraction, strengthens a role of Zscan4c in transcriptional regulation. Potential Zscan4c protein interaction partners were identified by applying a combined immunoprecipitation (IP) - mass spectrometry strategy. Interestingly, the majority of potential Zscan4c interacting proteins identified are associated with functions related to transcriptional regulation and DNA damage response, all characteristics linked with Zscan4. Furthermore, the Class IA PI3K catalytic isoforms were genetically activated in mES cells, and liberation of the requirement for LIF was found upon over-expression of an activated p110 catalytic subunit.

Subjects/Keywords: 616.02774; embryonic stem cells

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APA (6^th Edition):

Kumpfmueller, B. (2011). Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/control-of-embryonic-stem-cell-fate-the-role-of-phosphoinositide-3kinase-signalling-and-zscan4(439c6c52-1c06-4297-bd54-a97102875722).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550614

Chicago Manual of Style (16^th Edition):

Kumpfmueller, Benjamin. “Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4.” 2011. Doctoral Dissertation, University of Bath. Accessed March 06, 2021. https://researchportal.bath.ac.uk/en/studentthesis/control-of-embryonic-stem-cell-fate-the-role-of-phosphoinositide-3kinase-signalling-and-zscan4(439c6c52-1c06-4297-bd54-a97102875722).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550614.

MLA Handbook (7^th Edition):

Kumpfmueller, Benjamin. “Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4.” 2011. Web. 06 Mar 2021.

Vancouver:

Kumpfmueller B. Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4. [Internet] [Doctoral dissertation]. University of Bath; 2011. [cited 2021 Mar 06]. Available from: https://researchportal.bath.ac.uk/en/studentthesis/control-of-embryonic-stem-cell-fate-the-role-of-phosphoinositide-3kinase-signalling-and-zscan4(439c6c52-1c06-4297-bd54-a97102875722).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550614.

Council of Science Editors:

Kumpfmueller B. Control of embryonic stem cell fate : the role of phosphoinositide 3-kinase signalling and Zscan4. [Doctoral Dissertation]. University of Bath; 2011. Available from: https://researchportal.bath.ac.uk/en/studentthesis/control-of-embryonic-stem-cell-fate-the-role-of-phosphoinositide-3kinase-signalling-and-zscan4(439c6c52-1c06-4297-bd54-a97102875722).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550614

University of Edinburgh

5. Koutsouraki, Eirini. Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal.

Degree: PhD, 2015, University of Edinburgh

URL: http://hdl.handle.net/1842/21105

► Embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo and are characterized by the ability to self-renew and differentiate into… (more)

▼ Embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo and are characterized by the ability to self-renew and differentiate into all cell types of an adult organism, as demonstrated by their transplantation into embryos in the mouse. Isolation of cells with similar properties from human embryos has permitted the study of human cell differentiation in vitro as might occur during development. As such, human ES cells may be useful to assess and predict the developmental toxicity of environmental compounds capable of epigenetic alterations of the genome and its expression. The first objective of my research was to validate the functional significance to maintenance of an undifferentiated human ES cell state of expressed genes whose epigenetic modification is conserved across diverse lines and/or likely to be deterministic of an embryo stem cell associated epigenetic state. The second goal was to determine the sensitivity and relationship of the expression of these genes to environmental factors known to perturb the epigenome, specifically subcytotoxic exposure to diverse organic and metallic compounds and the availability of atmospheric oxygen. siRNA-mediated knockdown of genes previously identified on the basis of the conserved methylation status of gene associated Cytosine-Guanine islands (i.e. GLIS2, HMGA1, PFDN5, TET1 and JMJD2C) and two related family members (TET2 & 3) resulted in induction of cell differentiation in two independent human ES cell lines (RH1 and H9). Differentiation was reflected by morphological changes, reduction or loss of pluripotency associated markers, qualitative and quantitative reduction in genomic 5-hmC and upregulation of diverse germinal lineage markers. Subcytotoxic exposure of the same human ES cell lines to diverse compounds known to alter the epigenome (i.e. 5-azacytidine, sodium arsenite, cadmium chloride and valproic acid) generally induced downregulation of the aforementioned genes, loss of genomic hydroxymethylation and differentiation when applied under normoxia (20% O2), the exception being valproic acid. The same treatment applied under hypoxia (0.5% O2), did not induce differentiation, with the exception of cadmium chloride. Hypoxia is a general feature of developing embryos prior to the establishment of a maternal/fetal placental interface and fetal cardiovasculature. The protective effect of hypoxia was associated with elevation of ROS, expression of the dioxygenases TET1 and JMJD2C, and genomic hydroxymethylation. This research has demonstrated that genes identified on the basis of a conserved pattern of epigenetic modification function in the maintenance of an undifferentiated human ES cell phenotype. Furthermore, a human ES cell-based toxicology test system has been developed with which one can assess the subcytotoxic effects of compounds known to disrupt the epigenome and affect development by assessing their impact on maintenance of an undifferentiated human ES cell state. This is reflected by alterations in pluripotency markers,…

Subjects/Keywords: 616.02; epigenetics; toxicity; human embryonic stem cells; embryonic stem cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Koutsouraki, E. (2015). Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/21105

Chicago Manual of Style (16^th Edition):

Koutsouraki, Eirini. “Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed March 06, 2021. http://hdl.handle.net/1842/21105.

MLA Handbook (7^th Edition):

Koutsouraki, Eirini. “Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal.” 2015. Web. 06 Mar 2021.

Vancouver:

Koutsouraki E. Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1842/21105.

Council of Science Editors:

Koutsouraki E. Epigenetic and environmental determinants of undifferentiated human embryonic stem cell renewal. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/21105

Universiteit Utrecht

6. Kolijn, K. The origin and future of hematopoietic stem cells.

Degree: 2012, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/238606

► Hematopoietic stem cell (HSCs) therapy in the form of bone marrow transplantations has been used successfully in the clinic for over 40 years and continues… (more)

Subjects/Keywords: Hematopoietic stem cells; embryonic stem cells; induced pluripotent stem cells; ontogeny

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kolijn, K. (2012). The origin and future of hematopoietic stem cells. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/238606

Chicago Manual of Style (16^th Edition):

Kolijn, K. “The origin and future of hematopoietic stem cells.” 2012. Masters Thesis, Universiteit Utrecht. Accessed March 06, 2021. http://dspace.library.uu.nl:8080/handle/1874/238606.

MLA Handbook (7^th Edition):

Kolijn, K. “The origin and future of hematopoietic stem cells.” 2012. Web. 06 Mar 2021.

Vancouver:

Kolijn K. The origin and future of hematopoietic stem cells. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2021 Mar 06]. Available from: http://dspace.library.uu.nl:8080/handle/1874/238606.

Council of Science Editors:

Kolijn K. The origin and future of hematopoietic stem cells. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/238606

University of Cambridge

7. Schacker, Maria Anna. Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.35038 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763866

► Mouse embryonic stem (ES) cells have played a crucial role in studying developmental processes and gene function in vivo. They are extremely useful in the… (more)

▼ Mouse embryonic stem (ES) cells have played a crucial role in studying developmental processes and gene function in vivo. They are extremely useful in the generation of transgenic animals as they can be genetically manipulated and subsequently microinjected into blastocyst stage embryos, where they combine with the inner cell mass and contribute to the developing embryo. Some of the resulting pups are chimaeric, consisting of a mixture of cells derived from the host blastocyst and the injected ES cells. We have identified several ES cell clones arising from gene targeting experiments with an impaired capacity to generate viable chimaeras. When injected into blastocysts, these clones cause embryonic death during mid to late gestation, suggesting that the cells are able to contribute to the embryo but interfere with normal embryonic development. The aim of this work was to identify the underlying changes in the transcriptome, epigenome or cell surface markers that have occurred in these compromised ES cells and to further define the developmental phenotype of the chimaeric embryos. Different stages during development were analysed and whereas there was little difference in embryonic death at gestational day e13.5, there was a significant decrease in embryos surviving to gestational day e17.5. Additionally, severe haemorrhaging was observed in all the dead embryos and small foci of haemorrhaging could also be seen in a number of embryos that were still alive. This was also observed at e13.5, albeit to a less severe extent. Using RNA sequencing to discover differences in the transcriptome between control ES cells and the compromised ES cells, five genes were identified that were downregulated in the compromised cells. Four of these, Gtl2, Rtl1as, Rian and Mirg are all located in the imprinted Dlk1-Dio3 region on chromosome 12 and are normally expressed from the maternal genome. This pattern was also validated in tissues from e17.5 chimaeric embryos. The expression of this locus is to a large extent regulated by a differentially methylated region located approximately 13kb upstream of the Gtl2 promoter, the IG-DMR. Whereas this is usually only methylated on the paternal copy, in the compromised ES cells both the paternal and the maternal copy were fully methylated, likely causing the silencing of Gtl2, Rtl1as, Rian and Mirg. Using the DNA methyltransferase inhibitor 5-azacytidine, expression of Gtl2 could be rescued. Injection of those 5-azacytidine treated cells into blastocysts did partially rescue the embryonic lethal phenotype. Additionally, cell surface markers were analysed in a phenotypic screen using phage display. NGS analysis of the phage outputs indicates that there may be additional differences in cell surface markers between the control and compromised ES cell clones, but their specific details remain to be identified. Overall, we have identified the maternally expressed genes of the Dlk1-Dio3 region as markers that can distinguish between ES cells with normal or compromised developmental potency and propose…

Subjects/Keywords: 616.02; Embryonic Stem Cells; Epigenetics; Transcriptomics; Embryonic Development; Mouse Embryonic Stem Cells

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APA (6^th Edition):

Schacker, M. A. (2019). Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.35038 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763866

Chicago Manual of Style (16^th Edition):

Schacker, Maria Anna. “Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 06, 2021. https://doi.org/10.17863/CAM.35038 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763866.

MLA Handbook (7^th Edition):

Schacker, Maria Anna. “Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency.” 2019. Web. 06 Mar 2021.

Vancouver:

Schacker MA. Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 06]. Available from: https://doi.org/10.17863/CAM.35038 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763866.

Council of Science Editors:

Schacker MA. Defining the transcriptional and epigenetic signature of mouse embryonic stem cells with compromised developmental potency. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.35038 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763866

University of Aberdeen

8. Rore, Holly M. In vitro generation of male germ cell-like cells from mouse embryonic stem cells.

Degree: PhD, 2019, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970710005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774058

► Although methods of assisted reproduction are viable treatments for infertility, they are not always possible for azoospermic men. However, the use of stem cells may… (more)

▼ Although methods of assisted reproduction are viable treatments for infertility, they are not always possible for azoospermic men. However, the use of stem cells may provide an alternative means of generating sperm for treatment. To date, primordial germ cell-like cells (PGCLCs) have been produced in culture from mouse and human pluripotent stem cells (PSCs). However, these cells cannot undergo later stages of spermatogenesis unless transplanted into the testes. The implication is that the development of functional sperm requires the testis niche, primarily established by Sertoli cells. In terms of a therapeutic solution, the generation of Sertoli cell-like cells (SCLCs) by PSC differentiation is one means of recreating the testis niche and inducing maturation among PGCLCs in vitro. Drawing from knowledge of gonadogenesis, this thesis demonstrates a method of generating SCLCs entirely in vitro. Mouse PSCs were sequentially induced to form intermediate mesoderm, SCLCs and steroidogenic cells by addition of growth factors BMP7 and FGF9, and small molecules TTNPB (a retinoic acid receptor agonist) and CHIR99021 (a GSK3 inhibitor). These cells were found to endogenously express transcription factors critical for male development. Over-expression of one factor in particular, Steroidogenic factor-1 (SF1), substantially increased induction efficiency. Intriguingly, conditioned medium derived from SCLCs was also capable of specifying germ cell-like cells from Epiblast-like cells (EpiLCs), possibly due to the presence of key inducer BMP4. Co-culture of SCLCs and EpiLCs resulted in the formation of 'testicular organoids' reminiscent of the seminiferous tubules. These organoids were even capable of upregulating meiotic marker Stra8 in the presence of retinoic acid, suggesting that subsequent stages of maturation may have been achieved. On the whole, this study constitutes a significant step towards the use of PSCs to recreate spermatogenesis and testicular cell interactions in vitro, and serves as a useful basis for further investigations into the role of SF1 in Sertoli cell differentiation and function.

Subjects/Keywords: Embryonic stem cells; Sertoli cells; Mice

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APA (6^th Edition):

Rore, H. M. (2019). In vitro generation of male germ cell-like cells from mouse embryonic stem cells. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970710005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774058

Chicago Manual of Style (16^th Edition):

Rore, Holly M. “In vitro generation of male germ cell-like cells from mouse embryonic stem cells.” 2019. Doctoral Dissertation, University of Aberdeen. Accessed March 06, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970710005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774058.

MLA Handbook (7^th Edition):

Rore, Holly M. “In vitro generation of male germ cell-like cells from mouse embryonic stem cells.” 2019. Web. 06 Mar 2021.

Vancouver:

Rore HM. In vitro generation of male germ cell-like cells from mouse embryonic stem cells. [Internet] [Doctoral dissertation]. University of Aberdeen; 2019. [cited 2021 Mar 06]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970710005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774058.

Council of Science Editors:

Rore HM. In vitro generation of male germ cell-like cells from mouse embryonic stem cells. [Doctoral Dissertation]. University of Aberdeen; 2019. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970710005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774058

Michigan State University

9. Parenti, Anthony M. Making mammalian stem cells : identifying and overcoming reprogramming barriers.

Degree: 2016, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:4334

►

Thesis Ph. D. Michigan State University. Cell and Molecular Biology 2016

The field of stem cell biology had its first major boon when embryonic stem… (more)

▼

Thesis Ph. D. Michigan State University. Cell and Molecular Biology 2016

The field of stem cell biology had its first major boon when embryonic stem cells (ESCs) were derived from a mouse blastocyst in the 1980’s. ESCs have the potential to form any type of cell in the body, and thus represent a powerful new tool to study and treat a number of diseases that plague modern society. Despite the potential advantages ESCs offer, an embryo is destroyed in the derivation process, which leads to many ethical objections. Further, ESCs are not an exact genetic match to the patient they would be put into, which may lead to problems of graft rejection like we observe with organ transplantation. In 2006, a group of scientists made a revolutionary discovery when they expanded upon the trailblazing efforts of others, who employed somatic cell nuclear transfer and transcription factor based lineage conversion, to discover that a fully differentiated cell could be driven back to an embryonic state through forced expression of four transcription factors: Oct4, Sox2, Klf4, and cMyc (OSKM). These induced pluripotent stem cells (iPSCs) can also become any type of cell in the body and are identical to ESCs in many ways, but have the advantage of being derived from the patient they would be put back into, and do not require the destruction of an embryo. iPSCs offer the ideal tool to study and treat many different diseases including. Alzheimer’s, Parkinson’s, diabetes, Huntington’s, and Huntington-Gilford Progeria Syndrome among many others. Despite the potential for iPSCs, they remain extremely hard to produce. Various reports have described “barriers to reprogramming” that inhibit the conversion of differentiated cells to iPSCs. In the chapters that follow, I present my work uncovering previously unknown barriers to iPSC reprogramming including the formation of a different stem cell type during OSKM mediated reprogramming. Further, I detail my findings that examine the impact of aging on iPSC reprogramming and my findings that cells derived from aged individuals are not rejuvenated during the iPSC reprogramming process as previously hypothesized, but instead maintain the functional defects of old cells. The work presented herein represents my efforts to uncover the mechanisms underlying OSKM reprogramming. Many previously-held conceptions about OSKM reprogramming are not supported by my findings and need to be reassessed. Further, my work should serve as the launching point for future studies aimed at improving iPSC reprogramming efficiency and quality.

Description based on online resource;

Advisors/Committee Members: Ralston, Amy, Arnosti, David, Floer, Monique, Knott, Jason, Latham, Keith.

Subjects/Keywords: Embryonic stem cells; Embryonic stem cells – Research; Stem cells; Stem cells – Research; Cellular biology; Developmental biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Parenti, A. M. (2016). Making mammalian stem cells : identifying and overcoming reprogramming barriers. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:4334

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Parenti, Anthony M. “Making mammalian stem cells : identifying and overcoming reprogramming barriers.” 2016. Thesis, Michigan State University. Accessed March 06, 2021. http://etd.lib.msu.edu/islandora/object/etd:4334.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Parenti, Anthony M. “Making mammalian stem cells : identifying and overcoming reprogramming barriers.” 2016. Web. 06 Mar 2021.

Vancouver:

Parenti AM. Making mammalian stem cells : identifying and overcoming reprogramming barriers. [Internet] [Thesis]. Michigan State University; 2016. [cited 2021 Mar 06]. Available from: http://etd.lib.msu.edu/islandora/object/etd:4334.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Parenti AM. Making mammalian stem cells : identifying and overcoming reprogramming barriers. [Thesis]. Michigan State University; 2016. Available from: http://etd.lib.msu.edu/islandora/object/etd:4334

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Riverside

10. Sparks, Nicole Renee. The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells.

Degree: Environmental Toxicology, 2018, University of California – Riverside

URL: http://www.escholarship.org/uc/item/32z2s123

► Cigarette smoke is a mixture of over 7000 toxic components with at least 69 smoke chemicals producing cancers, suggesting that smoking is harmful to smokers.… (more)

Subjects/Keywords: Toxicology; Human Embryonic Stem Cells; Osteoblast

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APA (6^th Edition):

Sparks, N. R. (2018). The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells. (Thesis). University of California – Riverside. Retrieved from http://www.escholarship.org/uc/item/32z2s123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sparks, Nicole Renee. “The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells.” 2018. Thesis, University of California – Riverside. Accessed March 06, 2021. http://www.escholarship.org/uc/item/32z2s123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sparks, Nicole Renee. “The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells.” 2018. Web. 06 Mar 2021.

Vancouver:

Sparks NR. The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells. [Internet] [Thesis]. University of California – Riverside; 2018. [cited 2021 Mar 06]. Available from: http://www.escholarship.org/uc/item/32z2s123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sparks NR. The Embryotoxic Effects of Harm Reduction Tobacco Products on Osteoblasts Developing from Human Embryonic Stem Cells. [Thesis]. University of California – Riverside; 2018. Available from: http://www.escholarship.org/uc/item/32z2s123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

11. Gaobotse, Goabaone. The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal.

Degree: 2015, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:265054

► Stem cell pluripotency and self-renewal are two important attributes of human embryonic stem cells which have led to enhanced interest in stem cell research. Understanding… (more)

▼ Stem cell pluripotency and self-renewal are two important attributes of human embryonic stem cells which have led to enhanced interest in stem cell research. Understanding the mechanisms that underlie the regulation and maintenance of these properties is imperative to the clinical application of stem cells. Pluripotency and self-renewal are regulated by different genes, transcription factors and other co-factors such as FoxD3 and Klf4. Oct4, Nanog and Sox2 are central to the stem cell regulatory circuitry. They form interactions with co-factors to promote cell proliferation and inhibit differentiation by negatively regulating differentiation markers. However, there are other novel pluripotency associated factors yet to be studied. In this study, bioinformatics and functional analyses were employed to identify a potential pluripotency gene called YY1AP1 from our lab’s pre-existing microarray data. YY1AP1, a transcription regulatory gene, showed consistent down-regulation with induced cell differentiation. It was further investigated. First, its co-localization with Oct4 in both hESCs and iPSCs was confirmed by immunofluorescence staining. Knockdown experiments were then performed on this gene to investigate effects of knocking it down on gene expression in hESCs. Knocked-down cells were characterized for markers of pluripotency and differentiation at the transcript level. Results showed a down-regulation of pluripotency genes with no specific promotion of any of the germ layer markers. Gene expression at the protein level in knocked down cells was then assessed for YY1AP1, and its binding partner YY1, and pluripotency markers. Results showed that proteins of YY1AP1, YY1, Oct4, Nanog and CTCF were down regulated while the tumour suppressor gene protein, p53, was up-regulated in YY1AP1 deficient stem cells. Protein to protein interaction studies showed that YY1AP1, YY1, Nanog and CTCF proteins directly interacted with each other. Differentiation of YY1AP1deficient cells into EBs led to an almost complete shutdown of all gene expression, an indication that the cells did not form ‘real’ EBs. Differentiation of YY1AP1 ablated cells did not support any lineage promotion either. These results suggest a potentially new role for YY1AP1 in proliferation and self-renewal of stem cells through its possible direct binding to CTCF or its indirect binding to CTCF in complex with YY1. Advisors/Committee Members: BOOT-HANDFORD, RAYMOND RP, Boot-Handford, Raymond, Kimber, Susan.

Subjects/Keywords: human Embryonic Stem Cells; Pluripotency; Self-Renewal

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gaobotse, G. (2015). The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:265054

Chicago Manual of Style (16^th Edition):

Gaobotse, Goabaone. “The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal.” 2015. Doctoral Dissertation, University of Manchester. Accessed March 06, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:265054.

MLA Handbook (7^th Edition):

Gaobotse, Goabaone. “The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal.” 2015. Web. 06 Mar 2021.

Vancouver:

Gaobotse G. The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal. [Internet] [Doctoral dissertation]. University of Manchester; 2015. [cited 2021 Mar 06]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:265054.

Council of Science Editors:

Gaobotse G. The Expression and Regulation of Genes Correlating with human Embryonic Stem Cell (hESC) Pluripotency and Self-Renewal. [Doctoral Dissertation]. University of Manchester; 2015. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:265054

University of Manchester

12. Miller, Duncan. Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm.

Degree: 2012, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:183379

► Targeted differentiation of human embryonic stem cells (hESCs) towards definitive endoderm (DE) is the first step in generating hepatic or pancreatic cell types with potential… (more)

▼ Targeted differentiation of human embryonic stem cells (hESCs) towards definitive endoderm (DE) is the first step in generating hepatic or pancreatic cell types with potential for clinical application. Characterisation and efficiency of DE differentiation is improving, however the specific effects of the different exogenous growth factors used, and the changing presence and activity of endogenous factors, are still not well understood. One such endogenous factor, the TGFβ ligand Nodal, is known to drive patterning and differentiation of the primitive streak and DE in the developing mouse embryo. The effect of Nodal signalling during hESC DE differentiation is unknown, and the common use of a related exogenous ligand Activin A may also serve to upregulate rather than simply mimic it. In order to explore this, Activin A differentiation of hESCs in defined culture conditions was analysed. The expression of characteristic mesendoderm and DE markers increased during Activin A treatment, which was significantly enhanced by the inclusion of exogenous Wnt3a. A maintained presence of the pluripotency factor Nanog was observed in most cells expressing markers of DE. The levels of Nodal and its co-receptor Cripto, which were raised during the early stage of Activin A treatment, were also marginally enhanced by Wnt3a, and evidence of Nodal endocytosis further suggested an active signalling presence. RNA interference (RNAi) of Nodal negatively affected both pluripotency maintenance during normal pluripotent culture, and the capacity to differentiate towards DE. Use of a Cripto blocking antibody also inhibited differentiation towards DE. The results strongly suggested the presence of Nodal signalling, as well as possible roles for Nanog, Wnt-related signalling, and Nodal signalling during Activin A-mediated DE differentiation. The results contribute to current understanding of how DE differentiation in hESCs is regulated. They also identify clear targets for further investigation, which would lead to improved characterisation and differentiation of DE from hESCs. Advisors/Committee Members: Kimber, Susan.

Subjects/Keywords: Embryonic Stem Cells; Definitive Endoderm; Nodal

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Miller, D. (2012). Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:183379

Chicago Manual of Style (16^th Edition):

Miller, Duncan. “Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm.” 2012. Doctoral Dissertation, University of Manchester. Accessed March 06, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:183379.

MLA Handbook (7^th Edition):

Miller, Duncan. “Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm.” 2012. Web. 06 Mar 2021.

Vancouver:

Miller D. Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Mar 06]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:183379.

Council of Science Editors:

Miller D. Nodal Signalling During Targeted Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm. [Doctoral Dissertation]. University of Manchester; 2012. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:183379

University of Ottawa

13. Dawson, Jennifer Elizabeth. Cardiac Tissue Engineering .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/20071

► The limited treatment options available for heart disease patients has lead to increased interest in the development of embryonic stem cell (ESC) therapies to replace… (more)

▼ The limited treatment options available for heart disease patients has lead to increased interest in the development of embryonic stem cell (ESC) therapies to replace heart muscle. The challenges of developing usable ESC therapeutic strategies are associated with the limited ability to obtain a pure, defined population of differentiated cardiomyocytes, and the design of in vivo cell delivery platforms to minimize cardiomyocyte loss. These challenges were addressed in Chapter 2 by designing a cardiomyocyte selectable progenitor cell line that permitted evaluation of a collagen-based scaffold for its ability to sustain stem cell-derived cardiomyocyte function (“A P19 Cardiac Cell Line as a Model for Evaluating Cardiac Tissue Engineering Biomaterials”). P19 cells enriched for cardiomyocytes were viable on a transglutaminase cross-linked collagen scaffold, and maintained their cardiomyocyte contractile phenotype in vitro while growing on the scaffold. The potential for a novel cell-surface marker to purify cardiomyocytes within ESC cultures was evaluated in Chapter 3, “Dihydropyridine Receptor (DHP-R) Surface Marker Enrichment of ES-derived Cardiomyocytes”. DHP-R is demonstrated to be upregulated at the protein and RNA transcript level during cardiomyogenesis. DHP-R positive mouse ES cells were fluorescent activated cell sorted, and the DHP-R positive cultured cells were enriched for cardiomyocytes compared to the DHP-R negative population. Finally, in Chapter 4, mouse ESCs were characterized while growing on a clinically approved collagen I/III-based scaffold modified with the RGD integrin-binding motif, (“Collagen (+RGD and –RGD) scaffolds support cardiomyogenesis after aggregation of mouse embryonic stem cells”). The collagen I/III RGD+ and RGD- scaffolds sustained ESC-derived cardiomyocyte growth and function. Notably, no significant differences in cell survival, cardiac phenotype, and cardiomyocyte function were detected with the addition of the RGD domain to the collagen scaffold. Thus, in summary, these three studies have resulted in the identification of a potential cell surface marker for ESC-derived cardiomyocyte purification, and prove that collagen-based scaffolds can sustain ES-cardiomyocyte growth and function. This has set the framework for further studies that will move the field closer to obtaining a safe and effective delivery strategy for transplanting ESCs onto human hearts.

Subjects/Keywords: Embryonic Stem Cells; Cardiomyocytes; Collagen Scaffolds

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dawson, J. E. (2011). Cardiac Tissue Engineering . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/20071

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dawson, Jennifer Elizabeth. “Cardiac Tissue Engineering .” 2011. Thesis, University of Ottawa. Accessed March 06, 2021. http://hdl.handle.net/10393/20071.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dawson, Jennifer Elizabeth. “Cardiac Tissue Engineering .” 2011. Web. 06 Mar 2021.

Vancouver:

Dawson JE. Cardiac Tissue Engineering . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10393/20071.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dawson JE. Cardiac Tissue Engineering . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/20071

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

14. Ryan, Tammy. Molecular Mechanisms of Myogenesis in Stem Cells .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/20150

► Embryonic stem cells (ESCs) represent a promising source of cells for cell replacement therapy in the context of muscle diseases; however, before ESC-based cell therapy… (more)

▼ Embryonic stem cells (ESCs) represent a promising source of cells for cell replacement therapy in the context of muscle diseases; however, before ESC-based cell therapy can be translated to the clinic, we must learn to modulate cell-fate decisions in order to maximize the yield of myocytes from this systems. In order to gain a better understanding of the myogenic cell fate, we sought to define the molecular mechanisms underlying the specification and differentiation of ESCs into cardiac and skeletal muscle. More specifically, the central hypothesis of the thesis is that myogenic signalling cascades modulate cell fate via regulation of transcription factors. Retinoic acid (RA) is known to promote skeletal myogenesis, however the molecular basis for this remains unknown. We showed that RA expands the premyogenic progenitor population in mouse stem cells by directly activating pro-myogenic transcription factors such as Pax3 and Meox1. RA also acts indirectly by activating the pro-myogenic Wnt signalling cascade while simultaneously inhibiting the anti-myogenic influence of BMP4. This ultimately resulted in a significant enhancement of skeletal myogenesis. Furthermore, we showed that this effect was conserved in human embryonic stem cells, with implications for directed differentiation and cell therapy. The regulation of cardiomyogenesis by the Wnt pathway was also investigated. We identified a novel interaction between the cardiomyogenic transcription factor Nkx2.5 and the myosin phosphatase (MP) enzyme complex. Interaction with MP resulted in exclusion of Nkx2.5 from the nucleus and inhibition of its transcriptional activity. Finally, we showed that this interaction was modulated by phosphorylation of the Mypt1 subunit of MP by ROCK, downstream of Wnt3a. Treatment of differentiating mouse ESCs with Wnt3a resulted in exclusion of Nkx2.5 from the nucleus and a subsequent failure to undergo terminal differentiation into cardiomyocytes. This likely represents part of the molecular basis for Wnt-mediated inhibition of terminal differentiation of cardiomyocytes. Taken together, our results provide novel insight into the relationship between myogenic signalling cascades and downstream transcription factors and into how they function together to orchestrate the myogenic cell fate in stem cells.

Subjects/Keywords: embryonic stem cells; myogenesis; transcription factor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ryan, T. (2011). Molecular Mechanisms of Myogenesis in Stem Cells . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/20150

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ryan, Tammy. “Molecular Mechanisms of Myogenesis in Stem Cells .” 2011. Thesis, University of Ottawa. Accessed March 06, 2021. http://hdl.handle.net/10393/20150.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ryan, Tammy. “Molecular Mechanisms of Myogenesis in Stem Cells .” 2011. Web. 06 Mar 2021.

Vancouver:

Ryan T. Molecular Mechanisms of Myogenesis in Stem Cells . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10393/20150.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ryan T. Molecular Mechanisms of Myogenesis in Stem Cells . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/20150

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Columbia University

15. Mumau, Melanie. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.

Degree: 2018, Columbia University

URL: https://doi.org/10.7916/D8WD5BGJ

► The decisions stem cells make impact both the development of adult vertebrates and systems within the body that require cellular replenishment to sustain life. Regardless… (more)

▼ The decisions stem cells make impact both the development of adult vertebrates and systems within the body that require cellular replenishment to sustain life. Regardless whether a stem cell remains quiescent, divides, differentiates, or undergoes apoptosis—these processes are precisely controlled by internal gene regulatory networks that are instructed by external stimuli. The exact mechanisms governing stem cell fate are not completely understood. These studies explore new ways in which cell fate is mediated. Through a study of mitochondrial content in human embryonic stem cells (hESCs) and their differentiated progeny, we discovered differences in mitochondrial morphologies. Mitochondria began as elongated and networked structures in self-renewing conditions and changed their shape after differentiation. The addition of external growth factors that direct hESCs toward the definitive endoderm (DE) lineage promoted mitochondrial fragmentation, which was mediated by the mitochondrial fission machinery. Globular, punctate mitochondria were observed prior to the induction of the DE-specific transcriptional program. Differentiation of hESCs to other lineages did not result in any mitochondrial shape changes. Thus, mitochondrial fission in differentiating hESCs, an internal cellular process, is induced by DE-inducing external stimuli, an effect that was lineage specific. In a second study, we investigated the role of the splenic environment in the development of the blood system—during hematopoiesis. The spleen made a distinct contribution to hematopoiesis, a process predominantly attributed to the bone marrow. We discovered a previously unidentified population of cells, uniquely represented in the mouse spleen that could develop into erythrocytes, monocytes, granulocytes, and platelets. These multipotent progenitors of the spleen (MPPS) expressed higher levels of the transcription factor, NR4A1 compared to their bone marrow counterparts and relied on NR4A1 expression to direct their cell fate. The activation of NR4A1 in MPPS biased their production of monocytes and granulocytes in vitro whereas NR4A1-deficient MPPS over-produced erythroid lineage cells in vivo. Together, these data suggest the splenic niche supports distinct myeloid differentiation programs of multi-lineage progenitors cells. Both studies identify new mechanisms by which external stimuli regulate internal mechanisms of cell fate. These insights provide a better understanding of stem and progenitor cell differentiation that have the potential to impact cellular replacement therapies.

Subjects/Keywords: Immunology; Hematopoiesis; Embryonic stem cells; Cytology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mumau, M. (2018). The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8WD5BGJ

Chicago Manual of Style (16^th Edition):

Mumau, Melanie. “The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.” 2018. Doctoral Dissertation, Columbia University. Accessed March 06, 2021. https://doi.org/10.7916/D8WD5BGJ.

MLA Handbook (7^th Edition):

Mumau, Melanie. “The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.” 2018. Web. 06 Mar 2021.

Vancouver:

Mumau M. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Mar 06]. Available from: https://doi.org/10.7916/D8WD5BGJ.

Council of Science Editors:

Mumau M. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8WD5BGJ

University of Adelaide

16. Thomas, Paul Quinton. Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas.

Degree: 1996, University of Adelaide

URL: http://hdl.handle.net/2440/18750

Aims to identify homeobox genes which may have a developmental role during early embryogenesis by the characterization of homeobox gene expression in undifferentiated ES cells, and in a range of differentiated ES cell derivatives. Advisors/Committee Members: Dept. of Biochemistry (school).

Subjects/Keywords: Embryonic stem cells.

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomas, P. Q. (1996). Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/18750

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Thomas, Paul Quinton. “Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas.” 1996. Thesis, University of Adelaide. Accessed March 06, 2021. http://hdl.handle.net/2440/18750.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Thomas, Paul Quinton. “Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas.” 1996. Web. 06 Mar 2021.

Vancouver:

Thomas PQ. Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas. [Internet] [Thesis]. University of Adelaide; 1996. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2440/18750.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Thomas PQ. Homeobox gene expression in murine embryonic stem cells / by Paul Quinton Thomas. [Thesis]. University of Adelaide; 1996. Available from: http://hdl.handle.net/2440/18750

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

17. Soteriou, Despina. Definition of the human embryonic stem cell niche in vitro.

Degree: PhD, 2012, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/definition-of-the-human-embryonic-stem-cell-niche-in-vitro(ebe6a857-7cf5-45a2-8235-206f293d3ded).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553392

► The unique pluripotent character of human embryonic stem cells (hESCs) places them in the forefront of scientific research, especially as they hold great promise for… (more)

▼ The unique pluripotent character of human embryonic stem cells (hESCs) places them in the forefront of scientific research, especially as they hold great promise for application in regenerative medicine, as well as drug discovery and toxicity analyses. Conventionally hESCs are cultured on mitotically inactivated mouse embryonic fibroblasts (MEFs) that are derived from E13.5 mouse embryos. One of the biggest challenges in the hESC field is the development of a reproducible and defined hESC culture system that would eliminate batch-to-batch variability of the MEFs as well as exposure to feeder cells that makes hESCs less applicable for clinical use. Previous studies have shown that maintenance of pluripotency can be achieved using Matrigel, a mixture of ECM components, or ECM derived from MEFs or human fibroblasts (Xu, et al., 2001, Klimanskaya, et al., 2005). Other groups have succeeded in culturing feeder-free hESCs by using extracellular matrix (ECM) proteins, such as fibronectin, vitronectin or laminin, as substrates for hESC culture in the absence of feeders, confirming that ECM plays a key role in maintaining hESC growth (Amit, et al., 2004, Braam, et al., 2008, Baxter, et al., 2009, Rodin, et al., 2010).The aim of this work was to investigate the ECM deposited by MEF feeder cells and to isolate and identify proteins in the ECM that support undifferentiated growth of hESCs in the absence of feeders. We have investigated whether matrices derived from different passage feeders differ in their ability to support pluripotency. I also assessed the integrin receptor profile of hESCs in order to define the mechanisms of ECM engagement. ECM was extracted from two strains of feeder cells, CD1 x CD1 and MF1 x CD1, at passages 4 (early passage), 9 and 14 (late passage), and assessed for its ability to support hESC self-renewal over at least 3 passages. Tandem mass spectrometry was used to analyse the ECM composition of each MEF line, thereby allowing a comparison between different passages and different cell lines. More than 100 proteins were identified for each sample, the majority of which were ECM proteins and shared between different passage feeders. As predicted, fibronectin, which is known to support hESC self-renewal was the most prevalent species in all MEF-derived matrices. Furthermore a proteomic analysis of matrix derived from hESCs cultured in feeder-free conditions on fibronectin coating substratum revealed a number of proteins shared between supportive MEF populations and hESC, suggesting other potential candidates that may either assist or interfere with the maintenance of pluripotent hESCs. Of the proteins identified fibrillin-1, perlecan, fibulin-2 were tested as substrates for culturing hESCs in the absence of feeders, with the prospect of developing an optimised feeder-free culturing system that uses a combination defined animal-free substrates. Finally this study sought to dissect the interaction between ECM and growth factors and how these extrinsic factors may affect self-renewal and maintenance of…

Subjects/Keywords: 616.02774; Human embryonic stem cells; Extracellular matrix

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Soteriou, D. (2012). Definition of the human embryonic stem cell niche in vitro. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/definition-of-the-human-embryonic-stem-cell-niche-in-vitro(ebe6a857-7cf5-45a2-8235-206f293d3ded).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553392

Chicago Manual of Style (16^th Edition):

Soteriou, Despina. “Definition of the human embryonic stem cell niche in vitro.” 2012. Doctoral Dissertation, University of Manchester. Accessed March 06, 2021. https://www.research.manchester.ac.uk/portal/en/theses/definition-of-the-human-embryonic-stem-cell-niche-in-vitro(ebe6a857-7cf5-45a2-8235-206f293d3ded).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553392.

MLA Handbook (7^th Edition):

Soteriou, Despina. “Definition of the human embryonic stem cell niche in vitro.” 2012. Web. 06 Mar 2021.

Vancouver:

Soteriou D. Definition of the human embryonic stem cell niche in vitro. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Mar 06]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/definition-of-the-human-embryonic-stem-cell-niche-in-vitro(ebe6a857-7cf5-45a2-8235-206f293d3ded).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553392.

Council of Science Editors:

Soteriou D. Definition of the human embryonic stem cell niche in vitro. [Doctoral Dissertation]. University of Manchester; 2012. Available from: https://www.research.manchester.ac.uk/portal/en/theses/definition-of-the-human-embryonic-stem-cell-niche-in-vitro(ebe6a857-7cf5-45a2-8235-206f293d3ded).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553392

University of Melbourne

18. GOH, HWEE NGEE. Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker.

Degree: 2012, University of Melbourne

URL: http://hdl.handle.net/11343/37642

► The definitive endoderm, one of the primary germ lineages generated during early development, is the forerunner cell population that contributes to the formation of the… (more)

▼ The definitive endoderm, one of the primary germ lineages generated during early development, is the forerunner cell population that contributes to the formation of the gastrointestinal and respiratory tract and their associated organs such as liver and pancreas. The ability to form therapeutically useful cells such as hepatic and pancreatic cells on a large scale, in vitro, is envisaged to benefit regenerative medicine and have potential applications in drug discovery and research. Several studies have shown that embryonic stem (ES) cells are a potential source from which definitive endoderm can be derived. Strategies that are currently employed to form definitive endoderm from ES cells often lead to the formation of a heterogeneous array of cells, including multiple extraembryonic endodermal cell types. Isolation of definitive endoderm for further manipulation is hampered by the lack of specific gene markers. The realisation of the vision to form an ample amount of definitive endoderm for therapeutic and commercial use, relies on the ability to steer the differentiation of ES cells towards definitive endoderm lineages and the ability to identify and isolate these cells for further manipulation. The present three-part study aims to improve current methods of definitive endoderm formation and recognition through the use of an alternative model of definitive endoderm differentiation and identification of novel definitive endoderm markers that recognise specific subsets of definitive endoderm. Characterisation of the endoderm populations of a previously established in vitro model of differentiation known as embryoid bodies derived from early primitive ectoderm-like cells (EPLEBs), by gene expression, cellular morphology and function has demonstrated that endoderm formed in EPLEBs comprises definitive endoderm in the near absence of visceral endoderm. The absence of visceral endoderm in EPLEBs eliminates the inherent difficulties to distinguish between definitive endoderm derivatives from visceral endoderm formed in culture and removes confounding inductive signals that originate from the visceral endoderm. Formation of definitive endoderm within a less complex cellular environment in EPLEBs will facilitate analysis of molecular mechanisms that underpin the formation of definitive endoderm and these cellular aggregates will serve as a source of definitive endoderm from which novel definitive endoderm gene markers can be identified. Fate mapping studies in mice have shown that regionalisation of the definitive endoderm into discrete domains with different developmental potential is apparent prior to gut tube formation. At present, there is a significant shortage in regionally-specified genes that can be used to genetically identify and track the fate of specific subsets of definitive endoderm in gastrulating embryos. The paucity of regionally-specified gene markers has prompted the identification of novel definitive endoderm…

Subjects/Keywords: embryonic stem cells; definitive endoderm; developmental biology

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APA (6^th Edition):

GOH, H. N. (2012). Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/37642

Chicago Manual of Style (16^th Edition):

GOH, HWEE NGEE. “Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker.” 2012. Doctoral Dissertation, University of Melbourne. Accessed March 06, 2021. http://hdl.handle.net/11343/37642.

MLA Handbook (7^th Edition):

GOH, HWEE NGEE. “Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker.” 2012. Web. 06 Mar 2021.

Vancouver:

GOH HN. Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker. [Internet] [Doctoral dissertation]. University of Melbourne; 2012. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/11343/37642.

Council of Science Editors:

GOH HN. Characterisation of a novel in vitro model of definitive endoderm development and a novel definitive endoderm gene marker. [Doctoral Dissertation]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/37642

University of Southern California

19. Pomeroy, Jordan Elliott. Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions.

Degree: PhD, Systems Biology and Disease, 2012, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/20555/rec/1847

► Future use of pluripotent cells for regenerative medicine will require the derivation and characterization of new cell lines in clinical grade conditions. Removing potential sources… (more)

▼ Future use of pluripotent cells for regenerative medicine will require the derivation and characterization of new cell lines in clinical grade conditions. Removing potential sources of contamination, such as cell culture components sourced from animals, will aid the regulatory approval for future stem cell based therapeutics. In this dissertation, I describe the development of a xenobiotic-free cell culture system for the derivation and maintenance of human pluripotent cell lines. I have derived >40 hiPSC lines and one hESC line in the xeno-free cell culture conditions with maintenance of pluripotency charcacterized by morphology and immunocytochemistry marker expression for >50 passages and >30 passages respectively. The hESC line, USC-01 and several hiPSC lines derived for this study demonstrate highly similar gene expression patterns although slight differences are apparent. USC-01 and several hiPSC lines demonstrate the ability to differentiate into cells displaying characteristics of all three germ layers in an embryoid body differentiation assay. Further examination of the process of reprogramming somatic cells to a pluripotent state at both the RNA and protein expression levels indicates several genes/markers selective for hiPSCs achieving a pluripotent state most similar to the “gold-standard” of pluripotency possessed by hESCs. This study confirms the usefulness of the markers TRA-1-60, E-Cadherin and EpCAM for live-cell selection of the best hiPSC colonies and also demonstrates the usefulness of the marker GCTM-2. Expression analysis of colonies undergoing reprogramming also indicates that the genes FOXD3, CDH3, LCK, EDNRB, EPHA1, SOX2, and HAS3 are active in only a small subset of colonies 30 days after transfection of the piggyBac transposon reprogramming cassette. Since these genes are active in all hESC and most hiPSC positive control lines tested, confirmation of their activation could be used to select reprogramming hiPSC colonies most likely to achieve a pluripotent state similar to hESCs. Increased selection and derivation efficiencies of hiPSC lines demonstrating high fidelity to the hESC pluripotent state will streamline the generation of hiPSC lines for future testing as a replacement for hESCs in regenerative medicine. Advisors/Committee Members: Pera, Martin F. (Committee Chair), Ying, Qi-Long (Committee Member), Lu, Wange (Committee Member), Chuong, Cheng-Ming (Committee Member).

Subjects/Keywords: embryonic; stem; induced; pluripotent; cells; clinical; human

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APA (6^th Edition):

Pomeroy, J. E. (2012). Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/20555/rec/1847

Chicago Manual of Style (16^th Edition):

Pomeroy, Jordan Elliott. “Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions.” 2012. Doctoral Dissertation, University of Southern California. Accessed March 06, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/20555/rec/1847.

MLA Handbook (7^th Edition):

Pomeroy, Jordan Elliott. “Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions.” 2012. Web. 06 Mar 2021.

Vancouver:

Pomeroy JE. Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions. [Internet] [Doctoral dissertation]. University of Southern California; 2012. [cited 2021 Mar 06]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/20555/rec/1847.

Council of Science Editors:

Pomeroy JE. Derivation and characterization of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells in clinical grade conditions. [Doctoral Dissertation]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/20555/rec/1847

20. Morgani, Sophie Maria. Signalling and transcriptional regulation of early developmental lineage decisions.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/9660

► Embryonic stem (ES) cells are cell lines isolated from the embryo at a time just prior to implantation into the uterus. In the right cocktail… (more)

▼ Embryonic stem (ES) cells are cell lines isolated from the embryo at a time just prior to implantation into the uterus. In the right cocktail of medium and cytokines, these cell lines can be maintained indefinitely in vitro in a self-renewing state. Initially it was assumed that these cells represented a homogeneous population however, more recently it has been shown that there are a great number of genes that are expressed heterogeneously. ES cell cultures are therefore a mix of different subpopulations, some of which have distinct functional properties including a bias or ‘lineage priming’ towards a particular cell fate. These populations are also dynamic in nature, converting from one state to another with fairly rapid kinetics. The main focus of this thesis was to gain a more in depth understanding of the mechanisms regulating heterogeneity and lineage priming in murine ES cells by asking which signalling pathways play a role in this phenomenon and how the switch between states is regulated at a transcriptional level. These questions were asked using an ES cell line containing a sensitive reporter for the endoderm marker Hex. This reporter, developed by a previous lab member, allowed the identification and separation of a population of ES cells primed towards a primitive endoderm fate. Primarily, I assessed the effect of a defined culture system (2i) on the Hex-expressing population. This culture system contains inhibitors that block FGF signalling and the Wnt pathway component GSK3. Culturing ES cells in 2i has been suggested to generate a more homogeneous culture. Here, I have shown that culturing ES cells or pre-implantation embryos in 2i did not eliminate heterogeneity but maintained them in an early state prior to lineage segregation. When ES cells were cultured in standard serum-containing medium, Hex was expressed in a mutually exclusive manner with the embryonic marker NANOG, while in 2i a subpopulation of cells coexpressed both Hex and NANOG. This population was functionally primed towards extraembryonic endoderm and trophoblast. Furthermore, these ES cells could efficiently contribute to 2-cell embryos in chimaera assays. LIF signalling promoted this population through the JAK/STAT pathway. I then asked how transcription was regulated during the switch between unprimed ES cells to those primed towards a primitive endoderm fate, as well as how regulation changes during further differentiation. To ask this, Hex positive (primed) and negative (unprimed) ES cell populations were sorted as well as a Hex positive differentiated sample. These samples were analysed by GRO-seq to determine the location, density and orientation of RNA-polymerase throughout the genome. Changes in gene expression between primed and unprimed states were regulated primarily through elongation whereas genes upregulated during differentiation were regulated at the point of de novo initiation.

Subjects/Keywords: 616.02; developmental biology; embryonic stem cells

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APA (6^th Edition):

Morgani, S. M. (2014). Signalling and transcriptional regulation of early developmental lineage decisions. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/9660

Chicago Manual of Style (16^th Edition):

Morgani, Sophie Maria. “Signalling and transcriptional regulation of early developmental lineage decisions.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed March 06, 2021. http://hdl.handle.net/1842/9660.

MLA Handbook (7^th Edition):

Morgani, Sophie Maria. “Signalling and transcriptional regulation of early developmental lineage decisions.” 2014. Web. 06 Mar 2021.

Vancouver:

Morgani SM. Signalling and transcriptional regulation of early developmental lineage decisions. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1842/9660.

Council of Science Editors:

Morgani SM. Signalling and transcriptional regulation of early developmental lineage decisions. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/9660

Universitat de Valencia

21. Kostic, Jelena. Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol .

Degree: 2012, Universitat de Valencia

URL: http://hdl.handle.net/10550/25145

► Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic… (more)

▼ Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effects of ethanol Thesis: Jelena Kostic The main objective of this work is to use human neuroprogenitors (hNPs) cells from hESC as a tool to study the cellular and molecular events involved in early human neural development under physiological conditions and to study the teratogenic effects of ethanol during the initial formation of the CNS. Specific objectives include: Objectives - Development of an in vitro protocol of derivation of human neural progenitors (hNPs) from hESCs, which could mirror early stages of human brain development - Characterize the in vitro culture by evaluating the gene and protein expression of human Neuroprogenitors (hNPs) in culture during their proliferation and differentiation into mature cells (neurons, astrocytes and oligodendrocytes). - Assess whether the endocannabinoid system, including endocannabinoid receptors (CB1, CB2) and the enzymes involved in their synthesis (NAPE-PLD) and degradation (FAAH) of endocannabinoids (EC), are expressed in human neural progenitors during their differentiation to mature nervous cells. - Assess the gene and protein expression of TLR4 and TLR2 receptors during neural differentiation from hESC (in vitro) and during brain ontogeny in mice. - Finally, the last objective will investigate the actions of ethanol on the proliferation and differentiation of hNPs. Specifically we will assess the effects of different physiological concentrations of ethanol on: 1) gene and protein expressions during the derivation of hESC to NPs: 2) the proliferation and cells survival of the hNPs, 3) the NPs differentiation processes to mature neural cells, by assessing gene and protein expressions and morphological alterations, 4) the expression of endocannabinoid system and TLR4 and TLR2 in hESC, hNPs and brain development in mice. Results In this work we demonstrated the generation of human neural progenitors (hNPs) and differentiated neurons, oligodendrocytes and astrocytes from human embryonic stem cells (hESC) which mimics early brain development in humans. Neuroepithelial progenitors display the morphological and functional characteristics of their embryonic counterparts and the proper timing of neurons and glial cells generation. Immunocytochemical and real time (RT)-polymerase chain reaction analyses reveal that cells appeared as clusters during neuroepithelial cell proliferation and that the genes associated with the neuroectodermal (Pax-6) and the endodermic (α-fetoprotein) lineages decreased in parallel to the upregulation of the genes of hNPs (nestin and Tuj1), followed by their differentiation into neurons (MAP-2+, GABA+), oligodendrocytes [galactocerebroside (GalC+)], and astrocytes (GFAP+). We further demonstrate, for the first time, that human NPs express the endocannabinoid receptors (CB1 and CB2) and the enzymes involved in endocannabinoids synthesis… Advisors/Committee Members: Guerri Sirera, Consuelo (advisor).

Subjects/Keywords: human embryonic stem cells; ethanol; neural development

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kostic, J. (2012). Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol . (Doctoral Dissertation). Universitat de Valencia. Retrieved from http://hdl.handle.net/10550/25145

Chicago Manual of Style (16^th Edition):

Kostic, Jelena. “Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol .” 2012. Doctoral Dissertation, Universitat de Valencia. Accessed March 06, 2021. http://hdl.handle.net/10550/25145.

MLA Handbook (7^th Edition):

Kostic, Jelena. “Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol .” 2012. Web. 06 Mar 2021.

Vancouver:

Kostic J. Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol . [Internet] [Doctoral dissertation]. Universitat de Valencia; 2012. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10550/25145.

Council of Science Editors:

Kostic J. Differentiation of human Embryonic Stem Cells (hESC) into neural progenitors as a tool to study both the pathways during early brain development and the neuroteratogenic effecys of ethanol . [Doctoral Dissertation]. Universitat de Valencia; 2012. Available from: http://hdl.handle.net/10550/25145

22. Hodgson, Andrew Christopher. Microfluidic devices for the investigation of pluripotency in embryonic stem cells.

Degree: PhD, 2017, University of Cambridge

URL: https://doi.org/10.17863/CAM.13821 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725576

► This thesis presents the development of microfluidic devices designed to facilitate research into mouse embryonic stem cells (ESCs). ESCs are a well-studied cell, largely due… (more)

▼ This thesis presents the development of microfluidic devices designed to facilitate research into mouse embryonic stem cells (ESCs). ESCs are a well-studied cell, largely due to their pluripotent nature, meaning they are able to differentiate into all cell types of the body and may self-renew indefinitely in appropriate culture conditions. ESCs, along with many other lines of biological enquiry, are increasingly studied with the use of micro uidic technology which enables fine tuning of physical and chemical environments unachievable on the macro scale. Two varieties of microfluidic technology are presented in this thesis, one for high- resolution mechanical phenotyping of ESCs and the second as a novel in-chip culturing platform to study cellular transitions. Chapter 1 presents a broad introduction to ESCs and biological enquiry with microfluidics, aimed to underpin the following Chapters. Chapters 2 and 3 present self-contained projects, thus each include a motivation and introduction section more specific than that presented in Chapter 1. These Chapters also contain their own methods, results and conclusion sections. Finally, Chapter 4 presents a summary of the work performed along with an outlook of upcoming investigations. In Chapter 2, I present a microfluidic device developed and utilised in collaboration with Christophe Verstreken (Department of Physics, University of Cambridge), which has been used to apply a mechanical stress to live cells enabling measurement of their nuclear deformability. The device facilitates detection of both nucleus and cytoplasm which can then be analysed with a custom-written MATLAB code. Quantitative measurements of nuclear sizes and strains of ESCs indicated a negative Poisson ratio for nuclei of cells cultured in specific medium conditions. Furthermore, we demonstrate that the device can be used to physically phenotype at high-throughput by detecting changes in the nuclear response after treatment with actin depolymerising and chromatin decondensing agents. Finally, we show the device can be used for biologically relevant high-resolution confocal imaging of cells under compression. The work from this chapter is presented in Hodgson et al. [1]. In Chapter 3, I present a novel microfluidic platform developed in collaboration with Prof. Austin Smith and Dr Carla Mulas (Centre for Stem Cell Research, Cambridge). The developed platform enables individual ESCs to be cultured under continued observation as they exit their pluripotent stem cell state. Each cell within the device may be extracted from the chip at any time for further investigation without disturbing other cells. Assessing the transition from the stem cell state in individual cells is paramount if we are to understand the mechanisms of pluripotency.

Subjects/Keywords: 532; Microfluidics; Embryonic Stem Cells; Pluripotency

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APA (6^th Edition):

Hodgson, A. C. (2017). Microfluidic devices for the investigation of pluripotency in embryonic stem cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.13821 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725576

Chicago Manual of Style (16^th Edition):

Hodgson, Andrew Christopher. “Microfluidic devices for the investigation of pluripotency in embryonic stem cells.” 2017. Doctoral Dissertation, University of Cambridge. Accessed March 06, 2021. https://doi.org/10.17863/CAM.13821 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725576.

MLA Handbook (7^th Edition):

Hodgson, Andrew Christopher. “Microfluidic devices for the investigation of pluripotency in embryonic stem cells.” 2017. Web. 06 Mar 2021.

Vancouver:

Hodgson AC. Microfluidic devices for the investigation of pluripotency in embryonic stem cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2017. [cited 2021 Mar 06]. Available from: https://doi.org/10.17863/CAM.13821 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725576.

Council of Science Editors:

Hodgson AC. Microfluidic devices for the investigation of pluripotency in embryonic stem cells. [Doctoral Dissertation]. University of Cambridge; 2017. Available from: https://doi.org/10.17863/CAM.13821 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725576

University of Georgia

23. Blackstone, Hope. Nanog modification and degradation in murine embryonic stem cells.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/24831

► Embryonic stem cells are pluripotent progenitors for virtually all cell types in our body and contain limitless potential for therapeutic use and regenerative medicine. Murine… (more)

Subjects/Keywords: Embryonic Stem Cells; Nanog; Pluripotency; Self-renewal

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Blackstone, H. (2014). Nanog modification and degradation in murine embryonic stem cells. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/24831

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Blackstone, Hope. “Nanog modification and degradation in murine embryonic stem cells.” 2014. Thesis, University of Georgia. Accessed March 06, 2021. http://hdl.handle.net/10724/24831.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Blackstone, Hope. “Nanog modification and degradation in murine embryonic stem cells.” 2014. Web. 06 Mar 2021.

Vancouver:

Blackstone H. Nanog modification and degradation in murine embryonic stem cells. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10724/24831.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Blackstone H. Nanog modification and degradation in murine embryonic stem cells. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/24831

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Sydney

24. Brigden, Kurt. Copper transporters in development .

Degree: 2017, University of Sydney

URL: http://hdl.handle.net/2123/17116

► Copper is an essential trace element serving as a cofactor for critical enzymes. Copper uptake occurs via two solute carriers; Copper transporter 1 (Ctr1) and… (more)

▼ Copper is an essential trace element serving as a cofactor for critical enzymes. Copper uptake occurs via two solute carriers; Copper transporter 1 (Ctr1) and Copper transporter 2 (Ctr2). The high affinity transporter, Ctr1, is crucial for embryonic development. Ctr1 null-mutant mice die in utero from a gastrulation defect. This inability to generate mesoderm has been phenocopied in in vitro differentiation cultures of Ctr1-/- embryonic stem (ES) cells. However, the role of copper transporters during development remains unknown. In this thesis we aim to elucidate the roles of Ctr1 and Ctr2 during murine development. In sperm, Ctr2 was found expressed on the acrosomal cap, whilst Ctr1 was expressed in the cytoplasmic droplet. In the preimplantation embryo, Ctr1+ particles coalesced during cleavage stages, whilst Ctr2 colocalised with Keratin-8+ trophectoderm on the surface of the morula and blastocyst. The effect of copper on development of the preimplantation embryo cultured in vitro. Addition of copper sulfate proved lethal at concentrations greater that 50 μM. Copper chelation with tetrathiomolybdate resulted developmental arrest at concentrations greater than 1 μM. To assess copper transport to the post-implantation embryo we assessed the extra-embryonic tissues, the yolk sac and the placenta. The placenta was the primary site of copper transport with Ctr2 expressed on the maternal and foetal vessels between E10.5 – E16.5, while Ctr1 was expressed at E14.5. In the yolk sac Ctr2 was expressed in the visceral endoderm from E8.5 – E18.5. We next assessed the role of Ctr1 in germ layer specification utilising in vitro differentiation of Ctr1-null embryonic stem (ES) cells. During neurectoderm differentiation, loss of Ctr1 resulted in a lineage bias towards surface ectoderm. Absence of Ctr1 did not affect the ability of Ctr1-/- ES cells to generate CXCR4+c-Kit+ definitive endoderm or PECAM- PDGRFα+ extra embryonic endoderm relative to Ctr1+/+ ES cells. In addition, the mitochondrial reactive oxygen species probe, NpFR2, revealed that decreased mitochondrial activity in the absence of Ctr1 inhibits mesoderm formation. These findings better elucidate expression of copper transporters, Ctr1 and Ctr2, in delivery mechanisms of copper to the developing embryo as well as characterise the role of Ctr1 during germ layer specification.

Subjects/Keywords: Copper; Transport; Embryonic stem cells; Development

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Brigden, K. (2017). Copper transporters in development . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/17116

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Brigden, Kurt. “Copper transporters in development .” 2017. Thesis, University of Sydney. Accessed March 06, 2021. http://hdl.handle.net/2123/17116.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Brigden, Kurt. “Copper transporters in development .” 2017. Web. 06 Mar 2021.

Vancouver:

Brigden K. Copper transporters in development . [Internet] [Thesis]. University of Sydney; 2017. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2123/17116.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Brigden K. Copper transporters in development . [Thesis]. University of Sydney; 2017. Available from: http://hdl.handle.net/2123/17116

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

25. Miller, Duncan. Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm.

Degree: PhD, 2013, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/nodal-signalling-during-targeted-differentiation-of-human-embryonic-stem-cells-towards-definitive-endoderm(f468aa48-0830-42fe-98ee-1edff7ad1a5e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764265

► Targeted differentiation of human embryonic stem cells (hESCs) towards definitive endoderm (DE) is the first step in generating hepatic or pancreatic cell types with potential… (more)

▼ Targeted differentiation of human embryonic stem cells (hESCs) towards definitive endoderm (DE) is the first step in generating hepatic or pancreatic cell types with potential for clinical application. Characterisation and efficiency of DE differentiation is improving, however the specific effects of the different exogenous growth factors used, and the changing presence and activity of endogenous factors, are still not well understood. One such endogenous factor, the TGFβ ligand Nodal, is known to drive patterning and differentiation of the primitive streak and DE in the developing mouse embryo. The effect of Nodal signalling during hESC DE differentiation is unknown, and the common use of a related exogenous ligand Activin A may also serve to upregulate rather than simply mimic it. In order to explore this, Activin A differentiation of hESCs in defined culture conditions was analysed. The expression of characteristic mesendoderm and DE markers increased during Activin A treatment, which was significantly enhanced by the inclusion of exogenous Wnt3a. A maintained presence of the pluripotency factor Nanog was observed in most cells expressing markers of DE. The levels of Nodal and its co-receptor Cripto, which were raised during the early stage of Activin A treatment, were also marginally enhanced by Wnt3a, and evidence of Nodal endocytosis further suggested an active signalling presence. RNA interference (RNAi) of Nodal negatively affected both pluripotency maintenance during normal pluripotent culture, and the capacity to differentiate towards DE. Use of a Cripto blocking antibody also inhibited differentiation towards DE. The results strongly suggested the presence of Nodal signalling, as well as possible roles for Nanog, Wnt-related signalling, and Nodal signalling during Activin A-mediated DE differentiation. The results contribute to current understanding of how DE differentiation in hESCs is regulated. They also identify clear targets for further investigation, which would lead to improved characterisation and differentiation of DE from hESCs.

Subjects/Keywords: 616.02; Definitive Endoderm; Nodal; Embryonic Stem Cells

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APA (6^th Edition):

Miller, D. (2013). Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/nodal-signalling-during-targeted-differentiation-of-human-embryonic-stem-cells-towards-definitive-endoderm(f468aa48-0830-42fe-98ee-1edff7ad1a5e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764265

Chicago Manual of Style (16^th Edition):

Miller, Duncan. “Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm.” 2013. Doctoral Dissertation, University of Manchester. Accessed March 06, 2021. https://www.research.manchester.ac.uk/portal/en/theses/nodal-signalling-during-targeted-differentiation-of-human-embryonic-stem-cells-towards-definitive-endoderm(f468aa48-0830-42fe-98ee-1edff7ad1a5e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764265.

MLA Handbook (7^th Edition):

Miller, Duncan. “Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm.” 2013. Web. 06 Mar 2021.

Vancouver:

Miller D. Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Mar 06]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/nodal-signalling-during-targeted-differentiation-of-human-embryonic-stem-cells-towards-definitive-endoderm(f468aa48-0830-42fe-98ee-1edff7ad1a5e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764265.

Council of Science Editors:

Miller D. Nodal signalling during targeted differentiation of human embryonic stem cells towards definitive endoderm. [Doctoral Dissertation]. University of Manchester; 2013. Available from: https://www.research.manchester.ac.uk/portal/en/theses/nodal-signalling-during-targeted-differentiation-of-human-embryonic-stem-cells-towards-definitive-endoderm(f468aa48-0830-42fe-98ee-1edff7ad1a5e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764265

University of Toronto

26. Tewary, Mukul. Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/91995

► During embryogenesis, cells in different positions of the embryo acquire different fates in a seemingly autonomous process called ‘fate-patterning’. Fundamental studies have identified important signaling… (more)

▼ During embryogenesis, cells in different positions of the embryo acquire different fates in a seemingly autonomous process called ‘fate-patterning’. Fundamental studies have identified important signaling molecules (morphogens) that play crucial roles in coordinating developmental fate-patterning, examples include members of the transforming growth factor beta family – like bone morphogenetic proteins (BMPs), and Nodals. However, mechanistic understanding of how these morphogens coordinate fate-patterning remains unclear. Here we aim to apply bioengineering strategies to develop an in vitro model of developmental fate-patterning and employ it to interrogate the underlying mechanisms that govern this critical process. We first developed a robust, high-throughput platform to enable geometric-confinement of adherent cell types and employed it to screen various BMP4 supplemented defined media to identify conditions that coaxed geometrically-confined human pluripotent stem cell (hPSC) colonies to undergo peri-gastrulation-associated fate-patterning. This screen resulted in identification of defined conditions that spatially segregated compartments in the differentiating hPSC colonies expressing fate markers of trophoblast-like, primitive-streak-like, endoderm-like, mesoderm-like, and ectoderm-like tissues. Using a combination of experimental and computational-modelling approaches, we identified a stepwise mechanism of reaction-diffusion and positional-information underlying the observed peri-gastrulation-like fate-patterning. Here, a BMP4-Noggin reaction-diffusion network self-organized BMP signaling gradient, and this gradient patterned peri-gastrulation-associated fates in a manner consistent with positional-information. Furthermore, we found that Nodal signaling was necessary to induce the expression of the primitive-streak compartment – the precursor of gastrulation-derived fates. Interestingly, we also observed that Nodal signaling dissected gastrulation-associated and neurulation-associated gene expression profiles in differentiating hPSC lines. Specifically, in differentiating hPSCs, upregulation of Nodal signaling was observed in cells that upregulated a gene profile associated with gastrulation whereas absence of Nodal signaling correlated with upregulation of a neurulation-associated gene profile. We hypothesized that treatment of geometrically-confined hPSC colonies with BMP4 in the absence of Nodal signaling would induce fate patterning associated with neurulation. We observed experimental results consistent with this hypothesis and identified a conserved underlying mechanism of a stepwise model of reaction-diffusion and positional-information underlying the pre-neurulation-associated patterning as well. Taken together this work provides deep insight into how morphogens regulate early developmental stages of human embryogenesis – which have been previously inaccessible for experimentation. Advisors/Committee Members: Zandstra, Peter W, Biomedical Engineering.

Subjects/Keywords: Biomedical Engineering; Computational Modeling; Embryonic Development; Embryonic Stem Cells; Microfabrication; Pluripotent Stem Cells; 0541

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tewary, M. (2018). Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/91995

Chicago Manual of Style (16^th Edition):

Tewary, Mukul. “Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis.” 2018. Doctoral Dissertation, University of Toronto. Accessed March 06, 2021. http://hdl.handle.net/1807/91995.

MLA Handbook (7^th Edition):

Tewary, Mukul. “Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis.” 2018. Web. 06 Mar 2021.

Vancouver:

Tewary M. Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1807/91995.

Council of Science Editors:

Tewary M. Engineered In vitro models of post-implantation human development to elucidate mechanisms of self-organized fate specification during embryogenesis. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/91995

Georgia Tech

27. Sutha, Ken. Osteoinductive material derived from differentiating embryonic stem cells.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/51722

► The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function… (more)

▼ The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function of cells involved in bone formation but also to alterations in the bone microenvironment that occur through development and aging, including extracellular matrix (ECM) composition and growth/trophic factor content. In the development of novel treatments for bone repair, one potential therapeutic goal is the restoration of a more regenerative microenvironment, as found during embryonic development. One approach to creating such a microenvironment is through the use of stem cells. In addition to serving as a differentiated cell source, pluripotent stem cells, such as embryonic stem cells (ESCs), may possess the unique potential to modulate tissue environments via local production of ECM and growth factors. ESC-produced factors may be harnessed and delivered to promote functional tissue regeneration. Such an approach to generate a naturally derived, acelluar therapy has been employed successfully to deliver osteoinductive factors found within adult bone, in the form of demineralized bone matrix (DBM), but the development of treatments derived instead from developing, more regenerative tissues or cells remains attractive. Furthermore, the derivation of regenerative materials from an ESC source also presents the added benefit of eliminating donor to donor variability of adult, cadaveric tissue derived materials, such as DBM. Thus, the objective of this project was to examine the osteoinductive potential harbored within the embryonic microenvironment, in vitro and in vivo. The osteogenic differentiation of mouse ESCs as embryoid bodies (EBs) was evaluated in response to phosphate treatment, in vitro, including osteoinductive growth factor production. The osteoinductivity of EB-derived material (EBM) was then compared to that of adult tissue-derived DBM, in vivo. Phosphate treatment enhanced osteogenic differentiation of EBs. EBM derived from phosphate treated EBs retained bioactive, osteoinductive factors and induced new bone formation, demonstrating that the microenvironment within osteogenic EBs can be harnessed in an acellular material to yield in vivo osteoinductivity. This work not only provides new insights into the dynamic microenvironments of differentiating stem cells but also establishes an approach for the development of an ESC-derived, tissue specific therapy. Advisors/Committee Members: McDevitt, Todd C. (advisor), Guldberg, Robert E. (committee member), Schwartz, Zvi (committee member), Boyan, Barbara D. (committee member), O'Connell, Julie (committee member), Temenoff, Johanna S. (committee member).

Subjects/Keywords: Regenerative medicine; Regenerative therapy; Bone therapy; Embryonic stem cells; Embryonic stem cells; Bone regeneration

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sutha, K. (2012). Osteoinductive material derived from differentiating embryonic stem cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/51722

Chicago Manual of Style (16^th Edition):

Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Doctoral Dissertation, Georgia Tech. Accessed March 06, 2021. http://hdl.handle.net/1853/51722.

MLA Handbook (7^th Edition):

Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Web. 06 Mar 2021.

Vancouver:

Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1853/51722.

Council of Science Editors:

Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/51722

Universiteit Utrecht

28. Boer, A.S. de. iPS cell reprogramming.

Degree: 2009, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/35214

► Recently, pluripotent cells that are not derived from an embryo have been generated. These so called induced pluripotent stem cells (iPS cells) are pluripotent stem… (more)

Subjects/Keywords: Geneeskunde; embryonic stem cells, induced pluripotent stem cells, reprogramming, pluripotency, epigenetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Boer, A. S. d. (2009). iPS cell reprogramming. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/35214

Chicago Manual of Style (16^th Edition):

Boer, A S de. “iPS cell reprogramming.” 2009. Masters Thesis, Universiteit Utrecht. Accessed March 06, 2021. http://dspace.library.uu.nl:8080/handle/1874/35214.

MLA Handbook (7^th Edition):

Boer, A S de. “iPS cell reprogramming.” 2009. Web. 06 Mar 2021.

Vancouver:

Boer ASd. iPS cell reprogramming. [Internet] [Masters thesis]. Universiteit Utrecht; 2009. [cited 2021 Mar 06]. Available from: http://dspace.library.uu.nl:8080/handle/1874/35214.

Council of Science Editors:

Boer ASd. iPS cell reprogramming. [Masters Thesis]. Universiteit Utrecht; 2009. Available from: http://dspace.library.uu.nl:8080/handle/1874/35214

Univerzitet u Beogradu

29. Damjanović, Gordana M. Патентна заштита матичних ћелија.

Degree: Pravni fakultet, 2018, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:19048/bdef:Content/get

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Društvene nauke / Poslovno pravo Social sciences / business law

Биотехнологија и интелектуална својина јесу две области које су одиграле значајну улогу у трансформацији истраживања.… (more)

▼

Društvene nauke / Poslovno pravo Social sciences / business law

Биотехнологија и интелектуална својина јесу две области које су одиграле значајну улогу у трансформацији истраживања. Патентирање биотехнолошких проналазака јесте потребно првенствено због тога што се биотехнологија веома брзо развија, док се огромна средства која се улажу у истраживања и развој враћају веома споро. Предмет истраживања докторског рада обухватио је патентну заштиту матичних ћелија. Захваљујући истраживањима првенствено ембрионалних матичних ћелија, откривена су њихова два кључна својства која их чине изузетним, а то су: могућност гајења in vitro и плурипотентност. Новоткривена својства омогућују и нов приступ истраживању ћелија, њиховом развоју и поремећајима, попут ембрионалних тумора или урођених дефеката. Истраживања ће омогућити откривање нових лекова, а могуће је да ће се захваљујући истраживањима решити хронични недостатак ткива за трансплантацију, која се користе у лечењу дегенеративних болести. Као један од главних задатака 21. века наводи се - примена матичних ћелија у сврху продужетка живота. Ниједан биотехнолошки проналазак није изазвао толике расправе и дијаметрално супротне ставове као што је питање патентне заштите матичних ћелија. Различито правно третирање матичних ћелија у Европи у односу на Сједињене Америчке Државе, јесте последица разлика између патентног система Европе и Сједињених Америчких Држава. Већина европских патентних закона поседује такозвану моралну клаузулу, која омогућава надлежном органу да одбије патент на моралним основама, док у патентном систему Сједињених Америчких Држава морално вредновање нема формално место, већ се патентни испитивачи фокусирају на питања новости, инвентивности и индустријске применљивости, односно корисности. Сви релевантни прописи који су донети на тлу Европе дозвољајаву искључивање из патентибилности проналазака у циљу заштите морала и јавног интереса. Међутим, у погледу патентне заштите, првенствено ембрионалних матичних ћелија, не постоји консензус на тлу Европе. Посебно је сложено питање моралног статуса ембриона, јер ће ембрион, иако нема карактеристике личности ипак постати људско биће. Будући да су достигнућа у истраживању матичних ћелија оптерећена бројним не само правним, већ и етичким и религијским питањима, она су била предмет истраживања докторског рада. Правна теорија не даје дефиницију моралног статуса ембриона, због чега је истраживање било фокусирано и на питање: да ли је оправдано уништити ембрион и из њега деривирати ембрионалне матичне ћелије. С обзиром на то да се поштовање морала и људског достојанства може обезбедити не само ограничењима у оквиру патентног права, већ и етичком проценом проналазака током поступка патентирања, предмет истраживања је било и питање целисходности укључивања етичких одбора код процене патентибилности проналазака матичних ћелија.

Advisors/Committee Members: Marković, Slobodan M., 1956-.

Subjects/Keywords: biotechnology; patents; morality; human dignity; embryos; stem cells; embryonic stem cells.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Damjanović, G. M. (2018). Патентна заштита матичних ћелија. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:19048/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Damjanović, Gordana M. “Патентна заштита матичних ћелија.” 2018. Thesis, Univerzitet u Beogradu. Accessed March 06, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:19048/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Damjanović, Gordana M. “Патентна заштита матичних ћелија.” 2018. Web. 06 Mar 2021.

Vancouver:

Damjanović GM. Патентна заштита матичних ћелија. [Internet] [Thesis]. Univerzitet u Beogradu; 2018. [cited 2021 Mar 06]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:19048/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Damjanović GM. Патентна заштита матичних ћелија. [Thesis]. Univerzitet u Beogradu; 2018. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:19048/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin

30. Chung, HaeWon. Molecular mechanisms of mouse embryonic stem cell differentiation.

Degree: PhD, Cell and Molecular Biology, 2017, University of Texas – Austin

URL: http://hdl.handle.net/2152/61814

► Mouse embryonic stem (ES) cells are pluripotent cells, meaning that they can give rise to all tissues in the body. This has catalyzed research in… (more)

▼ Mouse embryonic stem (ES) cells are pluripotent cells, meaning that they can give rise to all tissues in the body. This has catalyzed research in both early embryogenesis as a model system for mammalian development as well as regenerative medicine as a renewable source of unspecialized cells which can be converted into nearly any cell type required by a patient. ES cells have been an invaluable resource for advancing fundamental understanding of global transcriptional and epigenetic regulations, signaling pathways, and noncoding RNA in mammalian systems. However, the molecular mechanisms of how ES cells are differentiated remain much less understood. Differentiation is a complex process involving actions of ES cell core factors, lineage specific regulators, epigenetic modifications, and chromatin remodelers. Thus, a single reporter-based screen would have been inappropriate to identify novel regulators of ES cell differentiation. To overcome the problems, we have developed a unique signature-based screen. This screen is capable of analyzing the expression of 48 genes simultaneously across dozens of different samples, and our gene list covers all three germ layers that arise during normal embryonic development, the trophectoderm, and epigenetic regulators of chromatin status. Our signature-based screen established several categories of genes based on their comparative functions during the differentiation of ES cells. This will be a valuable information for other researchers interested in ES cell differentiation from various perspectives. We have identified two novel regulators of ES cell differentiation – Yap1 and Rbpj. Yap1 is a transcriptional co-activator of Hippo signaling pathway. We disproved past misconceptions in the field about the role of Yap1 concerning its function in ES cell self-renewal, showing that like the inner cell mass, Yap1 is dispensable for long-term maintenance in culture. Conversely, we found that Yap1 is essential for proper ES cell differentiation. Rbpj is a transcriptional regulator of Notch signaling pathway. Consistent with previous observations of repressive role of Rbpj, Rbpj serves as a repressor of ES cell core factors in the absence of Notch signaling pathway. Repressive role of Rbpj is also required for proper differentiation of ES cells by silencing core factors. Advisors/Committee Members: Kim, Jonghwan, 1971- (advisor), Iyer, Vishwanath (committee member), Marcotte, Edward (committee member), Vokes, Steven (committee member), Ehrlich, Lauren (committee member).

Subjects/Keywords: Stem cells; Differentiation; Transcription factor; Embryonic stem cells

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APA (6^th Edition):

Chung, H. (2017). Molecular mechanisms of mouse embryonic stem cell differentiation. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/61814

Chicago Manual of Style (16^th Edition):

Chung, HaeWon. “Molecular mechanisms of mouse embryonic stem cell differentiation.” 2017. Doctoral Dissertation, University of Texas – Austin. Accessed March 06, 2021. http://hdl.handle.net/2152/61814.

MLA Handbook (7^th Edition):

Chung, HaeWon. “Molecular mechanisms of mouse embryonic stem cell differentiation.” 2017. Web. 06 Mar 2021.

Vancouver:

Chung H. Molecular mechanisms of mouse embryonic stem cell differentiation. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2017. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2152/61814.

Council of Science Editors:

Chung H. Molecular mechanisms of mouse embryonic stem cell differentiation. [Doctoral Dissertation]. University of Texas – Austin; 2017. Available from: http://hdl.handle.net/2152/61814

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