{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/97804"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/97804","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Transcriptional and epigenetic fluctuations in single cells","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_html":"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_has_math":false,"creators":["Klemm, Sandy Lee"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science.","school":null,"contributors":[],"advisors":["Alexander van Oudenaarden and Rudolf Jaenisch."],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015","date_published":"2015","updated_at":"2026-07-22T22:21:24Z","subjects":["Electrical Engineering and Computer Science."],"languages":["eng"],"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."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/97804","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Alexander van Oudenaarden and Rudolf Jaenisch."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science."]},{"key":"dc:creator","label":"Author","values":["Klemm, Sandy Lee"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-07-17T19:48:18Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-07-17T19:48:18Z"]},{"key":"dc:date.issued","label":"Date","values":["2015"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Electrical Engineering and Computer Science."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/97804"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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)."]},{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:title","label":"Title","values":["Transcriptional and epigenetic fluctuations in single cells"]}]}],"canonical_facts":{"dc:contributor.advisor":["Alexander van Oudenaarden and Rudolf Jaenisch."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science."],"dc:contributor.other":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science."],"dc:creator":["Klemm, Sandy Lee"],"dc:date.accessioned":["2015-07-17T19:48:18Z"],"dc:date.available":["2015-07-17T19:48:18Z"],"dc:date.issued":["2015"],"dc: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)."],"dc:description.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."],"dc:description.degree":["Ph. D."],"dc:identifier.uri":["http://hdl.handle.net/1721.1/97804"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"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."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Electrical Engineering and Computer Science."],"dc:title":["Transcriptional and epigenetic fluctuations in single cells"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:21:24Z"}