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Gene Expression Changes Associated with the Differentiation of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like Cells

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Abstract:
Embryonic stem cells (ESCs) are found early in the developing embryo and from this initial population, all cells in the body are eventually derived. A hallmark characteristic of ESCs is their pluripotent nature, which is established to a large extent by transcriptional regulation. The core transcription factor network commonly referred to in stem cell pluripotency includes Oct3/4, Sox2 and Nanog which then contribute to a vast protein interaction network. The process by which embryonic stem cells become differentiated into cells with novel characteristics is tightly regulated and specific. In the past several decades, there has been great interest regarding how mammalian ESCs might be cultured in vitro to promote the derivation of cell types for research as well as medical endeavors. Primordial germ cells, the precursors of gametes, are an especially interesting subject for differentiation as they are linked to ESCs via their reinstated pluripotency upon fertilization to divide and constitute a new organism. This thesis describes the theory and experimental methodology necessary to derive primordial germ cell-like cells (PGCLCs) from mouse embryonic stem cells (ESCs). Throughout this process, the optimal expansion and culture conditions of ESCs, epiblast-like cells (EpiLCs) and PGCLCs were implemented. A major initial goal was to assess the efficacy of differentiation via expected changes in gene expression throughout each differentiation step. Establishing this in vitro model system will then allow us to answer mechanistic questions about the how subunits of the core transcription factor TFIID complex may contribute to the maintenance of ESC pluripotency through the transcriptional network and how they change to regulate the pathway by which PGCLCs are specified.
Notes:
Thesis (Sc. M.)--Brown University, 2018

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Citation

Mori, Megumi, "Gene Expression Changes Associated with the Differentiation of Mouse Embryonic Stem Cells to Primordial Germ Cell-Like Cells" (2018). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/cyek-y927

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