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Stem Cells: Defining and Reprogramming a Neural Lineage

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Stem cells show great promise as cellular replacement and drug delivery therapies for a number of neurological disorders. This dissertation examines embryonic and adult types of stem cells, their plasticity, and mechanisms governing their development (Chapters 1-5). Our studies illustrate that leukemia inhibitory factor (LIF) signaling and bone morphogenetic protein (BMP) signaling are key regulators of neural stem cell (NSC) maintenance with opposing functions (Chapter 2). These signaling pathways generate discrete astroglial cell types previously thought to be identical, affect the size of the NSC pool, and control fate commitment during development. Further, we demonstrate that NSCs exist in the adult hippocampus (Chapter 3). BMP inhibition with noggin expands the adult NSC pool both in culture and in vivo. This expansion will serve as a useful paradigm to investigate factors regulating NSCs and the functional role of hippocampal neurogenesis. Finally, we use nuclear transfer to address the role of the donor cell epigenome in reprogramming (Chapter 4). We find within a neural lineage that reprogramming occurs less frequently in more differentiated cells. These results are important for the understanding of epigenetics and the production of autologous stem cells for potential therapy. Future studies, both planned and prospective, are discussed (Chapter 5) with emphasis placed on nuclear reprogramming

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  • 05/14/2018
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