Programming and reprogramming cellular identity

Every cell in the human body contains the same genetic information, with few exceptions, yet each cell type enacts a distinct gene expression program to allow for highly specialized functions. These tightly controlled programs are the results of transcriptional regulation, by transcription factors and chromatin regulators, as well as post-transcriptional regulation, mediated in part by microRNAs (miRNAs). Additionally, cells must respond to external cues, and signal transduction pathways converge on gene regulatory machinery to shape cellular identity. The work presented here focuses on the mechanisms by which transcription factors, chromatin regulators, miRNAs and signal transduction pathways coordinately regulate two particular medically important gene expression programs: (1) the program that controls pluripotency in embryonic stem (ES) cells, giving these cells the capacity to differentiate into every adult cell type, and (2) the program that allows regulatory T (Treg) cells to prevent autoimmunity by suppressing the response of self-reactive conventional T cells. Genomic investigations of the core regulatory circuitry of each of these cells types presented here provide new insight into the genetics of pluripotency and autoimmunity, and suggest a strategy for reprogramming based on chemical manipulation of the cellular programs that control cell identity.

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

• Marson, Alexander

Advisor dc:contributor.advisor

• Richard A. Young and Rudolf Jaenisch.

• 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/1721.1/43223

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43223