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Beta-catenin Associated Protein Complex Maintains Ground State Mouse Embryonic Stem Cell by Regulating Germline Development
dc.contributor.advisor | Li, Linheng | |
dc.contributor.author | Tao, Fang | |
dc.date.accessioned | 2017-08-13T21:01:26Z | |
dc.date.available | 2017-08-13T21:01:26Z | |
dc.date.issued | 2016-12-31 | |
dc.date.submitted | 2016 | |
dc.identifier.other | http://dissertations.umi.com/ku:15041 | |
dc.identifier.uri | http://hdl.handle.net/1808/24803 | |
dc.description.abstract | Mouse embryonic stem (ES) cells cultured in defined medium with MEK and GSK3 inhibitors(2i) resemble the pre-implantation epiblast in the ground state, with full development capacity including the somatic lineages and the germline. Although beta- catenin is known to be crucial for naive pluripotency of ES cells, the mechanism is not fully understood. Here I show that beta-catenin interacts with a repressive protein complex to maintain the ground state of ES cells by fine-tuning the germline development potential of ES cells. I use the mouse ES cell to show that absence of beta-catenin impairs ES cell self-renewal without affecting the core self-renewal circuitry of Oct4, Sox2 and Nanog as well as other pluripotency factors. However, beta-catenin-deficient cells show a primed state transcriptional signature with perturbed gene expression of germline and neuronal lineage. Knockdown of Tcf7l1, the repressor in canonical Wnt signaling pathway, does not completely rescue the beta-catenin-deficient phenotype of ES cells. Mechanistically, beta-catenin forms a novel biochemical complex with E2F6, HP1gamma and HMGA2 to restrain ES cells from differentiation by co-occupying the promoter of germline and neuronal lineage regulators independent of TCF7L1. Moreover, beta-catenin functions differentially in early and late germ cell development, and keeps balance with E2F6 to prevent premature meiosis initiation in ES cells. Overall, my study shows that beta-catenin forms a repressive protein complex with E2F6, HP1gamma and HMGA2 to maintain ground state by orchestrating the development plasticity of ES cells. | |
dc.format.extent | 98 pages | |
dc.language.iso | en | |
dc.publisher | University of Kansas | |
dc.rights | Copyright held by the author. | |
dc.subject | Developmental biology | |
dc.subject | Biochemistry | |
dc.subject | Cellular biology | |
dc.subject | differentiation | |
dc.subject | germline | |
dc.subject | ground state | |
dc.subject | mouse embryonic stem cell | |
dc.subject | pluripotency | |
dc.subject | Wnt/beta-catenin | |
dc.title | Beta-catenin Associated Protein Complex Maintains Ground State Mouse Embryonic Stem Cell by Regulating Germline Development | |
dc.type | Dissertation | |
dc.contributor.cmtemember | Soumen Paul, Soumen | |
dc.contributor.cmtemember | Slawson, Chad | |
dc.contributor.cmtemember | Zeitlinger, Julia | |
dc.contributor.cmtemember | Soares, Michael J | |
dc.contributor.cmtemember | Fields, Patrick E | |
dc.thesis.degreeDiscipline | Pathology & Laboratory Medicine | |
dc.thesis.degreeLevel | Ph.D. | |
dc.identifier.orcid | ||
dc.rights.accessrights | openAccess |
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Dissertations [4889]
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KU Med Center Dissertations and Theses [464]