2026-09-19T04:29:45Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/978042026-06-16T18:55:58Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Alexander van Oudenaarden and Rudolf Jaenisch.
Klemm, Sandy Lee
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science.
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
2015-07-17T19:48:18Z
2015-07-17T19:48:18Z
2015
2015
http://hdl.handle.net/1721.1/97804
912297340
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2015.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages [130]-140).
Fluctuations in the transcriptional and proteomic state of single cells is a common feature of living systems. The focus of this work is to understand the epigenetic orgin of this heterogeneity. For biochemical noise arising from the intrinsic stochasticity of molecular interactions, we have experimentally established a microRNA mediated mechanism through which epigenetically determined rate parameters are optimized to suppress noise in protein abundance. We further explore regulated fluctuations that confer phenotypic specificty in embryonic stem cells by isolating and genomically profiling cells in distinct molecular states. To achieve this, we have developed a fluorescent measure of RNA in single cells that facilitates high-resolution transcriptional sorting (RNA FACS) as well as subpopulation profiling of both chromatin and gene expression. Using this technique, we show that stochastic fluctuations in many pluripotency associated genes are driven by a coordinated program of cyclic methylation and demethylation that is widely distributed across the genome. We anticipate broad applicability of these results for studying epigenetic and transcriptional regulation in single cells.
by Sandy Lee Klemm.
Ph.D.
140 pages
eng
Massachusetts Institute of Technology
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.
http://dspace.mit.edu/handle/1721.1/7582
Electrical Engineering and Computer Science.
Transcriptional and epigenetic fluctuations in single cells
Thesis
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<Abstract>Fluctuations in the transcriptional and proteomic state of single cells is a common feature of living systems. The focus of this work is to understand the epigenetic orgin of this heterogeneity. For biochemical noise arising from the intrinsic stochasticity of molecular interactions, we have experimentally established a microRNA mediated mechanism through which epigenetically determined rate parameters are optimized to suppress noise in protein abundance. We further explore regulated fluctuations that confer phenotypic specificty in embryonic stem cells by isolating and genomically profiling cells in distinct molecular states. To achieve this, we have developed a fluorescent measure of RNA in single cells that facilitates high-resolution transcriptional sorting (RNA FACS) as well as subpopulation profiling of both chromatin and gene expression. Using this technique, we show that stochastic fluctuations in many pluripotency associated genes are driven by a coordinated program of cyclic methylation and demethylation that is widely distributed across the genome. We anticipate broad applicability of these results for studying epigenetic and transcriptional regulation in single cells.</Abstract>
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