Mapping the core regulatory circuitry of embryonic stem cells
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259222653-MIT.pdf
Description
Full printable version
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54.76 MB
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4d5751c533e3f1337d375ebd02714f4d
Author(s)
Johnstone, Sarah E
Advisor(s)
Richard A. Young.
Date Issued
2008
Publisher
Massachusetts Institute of Technology
Abstract
Embryonic stem (ES) cells are of tremendous biological interest because they have the capacity, termed pluripotency, to generate any cell type of the adult organism. Our lab is interested in understanding the genetic circuitry that governs pluripotency. For my thesis work I have contributed to a team effort to deduce the transcriptional regulatory circuitry of ES cells. This collaborative effort first sought to define the genes that are regulated by the key pluripotency regulators, Oct4, Sox2 and Nanog. We then determined the genes targeted by the Polycomb Repressive Complex in ES cells. These datasets allowed us to define the core transcriptional regulatory circuitry for these cells and demonstrated that pluripotency is mediated through the repression of developmental regulators. Finally, an effort to understand how Wnt signaling modifies this circuitry led to the discovery that the Wnt signaling component Tcf3 is a core component of the transcriptional regulatory circuitry and serves to repress the pluripotency regulators, contributing to the balance between pluripotency and differentiation.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.
Includes bibliographical references.
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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