Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 17 of 17 for “"definitive endoderm"”.
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FGF signaling in specification of hESC-derived definitive endoderm
… development. Pancreas originates from the definitive endoderm (DE), one of the three germ layers. The path from definitive endoderm to pancreatic progenitor cells and finally the insulin producing beta cells involves sequential cell-fate decisions characterized by the expression of multiple …
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Human Embryonic Stem Cells - Constitutive Gene Expression and Differentiation Towards Definitive Endoderm and Posterior Foregut Endoderm
… fundamental research tools. Identification of definitive endoderm (DE) - from where pancreas originates, requires analysis methods that can detect multiple markers within individual cells, since many markers expressed in DE are also detected in extraembryonic endoderm. In this thesis, we …
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The role of transcription factor GATA6 in the development of the human pancreas
… that GATA6 is required for the formation of the definitive endoderm (DE) and pancreas in humans; hPSCs harbouring homozygous GATA6 mutations fail to form the definitive endoderm, and consequently the pancreas, whereas hPSCs harbouring heterozygous GATA6 mutations exhibited impairment in …
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Directed differentiation of endodermal cells from mouse embryonic stem cells
… cyclopamine, an attempt has been made to produce definitive endoderm and subsequently cells that can serve as pancreatic and hepatocyte precursors from mouse embryonic stem cells. By using retinoic acid and basic-FGF, in the absence of embryoid body formation, mouse embryonic stem cells were …
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SMAD2/3 - FOXH1 regulation during cell cycle progression upon differentiation
… mediated by nocodazole with our well-established endoderm differentiation protocol to study the coordination between cell cycle and differentiation. This approach first revealed that the transition from pluripotency to definitive endoderm requires two cell cycles. I then focused on the forkhead …
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The effect of replication impediments on differentiation
… pluripotent stem cell line was differentiated to definitive endoderm while replication was perturbed using DNA damaging agents, low dose hydroxyurea and G-quadruplex secondary structure stabilisation. DNA damage was induced both in the undifferentiated state and during differentiation. When damage …
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Eomes Directs the Formation of Spatially and Functionally Diverse Extra-Embryonic Mesoderm Derived Tissues
… tissues, such as the trophectoderm, visceral and definitive endoderm, and various anterior mesodermal tissues. Additionally, Eomes has been implicated to be an important regulator of yolk-sac haematopoiesis, but was thought not to play a role in the development of yolk-sac endothelium. In Chapter …
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Characterizing the Immunogenicity of Islet-like Cells derived from HLA-edited Human Pluripotent Stem Cells
… the successive phenotypes of primitive streak, definitive endoderm, and pancreatic progenitors. I next explore mechanisms that regulate the endocrine composition of human pluripotent stem cell-derived islets, finding that events both prior to and concurrent with endocrine commitment have …
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Investigation of pancreatic beta cell differentiation and function, and global profiling analysis of diabetes serum for the identification of disease biomarkers
… 2D and 3D culture, with improved efficiency of definitive endoderm formation in 3D cultures (a step on the differentiation routetowards beta cells). In parallel, serum from diabetes patients was examined to identify new disease iomarkers in a collaborative clinical study with Connolly Hospital, …
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Mechanisms of Foregut Formation in Mus Musculus
… forms by the invagination of the anterior endoderm at embryonic day 7.5 and later gives rise to essential organs of the gastrointestinal and respiratory system. The formation of the foregut is critical for establishing the anterior organisation of the embryo, including the positioning of …
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Development of 3D multicellular liver organoids derived from human induced pluripotent stem cells to model antiretroviral therapy induced liver injury
… in pluripotency (OCT-4, Nanog, and Sox2) and the definitive endoderm (SOX17 and GSC) markers. Flow cytometry using EpCAM, CD166 and CD68 antibodies indicated that HLOs comprise of 60,4% EpCAM+ cells, 11,2% EpCAM-/CD166+ cells and 5% EpCAM-/CD68+ cells, respectively. HLOs exhibited high CYP3A4 …
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Theoretical and Computational Studies on the Dynamics and Regulation of Cell Phenotypic Transitions
… such a motif regulating the differentiation of definitive endoderm. We identified two RNA binding proteins, hnRNPA1 and KSRP, which repress each other through microRNAs miR-375 and miR-135a. The motif can generate switch behavior and serve as a noise filter in the stem cell differentiation …
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A chemical biology study of human embryonic stem cell pluripotency and differentiation
… of hESC differentiation towards the mesoderm and definitive endoderm (DE) lineages. Cell-replacement therapies require differentiated cells of high purity, yet current human pluripotent stem cell differentiation protocols remain to be improved for such purposes. I attempted to enhance the commonly …
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Investigation of genetic PIK3CA activation in genome-edited human pluripotent stem cells
… of PI3K signalling is fully compatible with definitive endoderm formation, arguing against cell-autonomous differentiation defects as the cause of endoderm sparing in PROS. In summary, these studies demonstrate the utility of human stem cell-based models of PROS for preclinical drug testing …
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An in vitro model of human yolk sac and epiblast crosstalk
… Within mouse development, the anterior visceral endoderm (AVE), formed from the extraembryonic endoderm, plays a crucial role in restricting primitive streak formation to the posterior epiblast, thereby establishing the anterior-posterior axis of the mouse embryo. Recent studies of human embryos …
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Encapsulation as a 3D model for human embryonic stem cell propagation and differentiation
… hESCs were successfully differentiated into definitive endoderm (DE); however, this 3D model was not efficient to derive functional beta cells due to low cell viability maintained during the latter differentiation stages. To enhance this differentiation process, further investigation was …
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DNA topology and Pol II CTD phosphorylation as stepwise regulators of chromatin architecture in differentiating human stem cells
… sequence alone. In this thesis, I establish definitive endoderm differentiation as a model system to investigate how such encoding might operate, focusing on two complementary ideas. The first is that changes in DNA topology reshape the binding landscape for Pol II and its regulators, through …