Transcriptional and epigenetic fluctuations in single cells
Name
912297340-MIT.pdf
Description
Full printable version
Size
22.88 MB
Format
Adobe PDF
Checksum (MD5)
68b11f21b936f336b340995b07c7233f
Author(s)
Klemm, Sandy Lee
Advisor(s)
Alexander van Oudenaarden and Rudolf Jaenisch.
Date Issued
2015
Publisher
Massachusetts Institute of Technology
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.
Description
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).
Subjects
Electrical Engineering and Computer Science.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
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