Mapping the core regulatory circuitry of embryonic stem cells

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Johnstone, Sarah E

Advisor dc:contributor.advisor

• Richard A. Young.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/43221

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43221