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dc.contributor.advisorMerrill, Bradley J.en_US
dc.contributor.authorHoffman, Jackson A.en_US
dc.date.accessioned2012-12-13T22:00:20Z
dc.date.available2012-12-13T22:00:20Z
dc.date.created2012-08en_US
dc.date.issued2012-12-13
dc.date.submitted2012-08en_US
dc.identifier.urihttp://hdl.handle.net/10027/9581
dc.description.abstractMy research has focused on elucidating the function of Tcf7l1 in embryonic stem cells (ESC) and the pluripotent cells of the mouse embryo. Previous work has revealed that Tcf7l1 is a component of the Oct4/Sox2/Nanog gene regulatory network (GRN) that regulates the pluripotency of ESC. My research has revealed that Tcf7l1 is a critical factor for coordinating the regulation of the pluripotency GRN with the onset of embryonic lineage specification. I found that Tcf7l1 was necessary for pluripotent cells to transition from a self-renewing state to a state that was primed for lineage specification. In the absence of Tcf7l1, this transition and subsequent lineage specification was delayed/defective. I was further able to show that this in vitro function was conserved during in vivo development of the mouse embryo. Tcf7l1-/- embryos exhibited prolonged and un-regulated expression of pluripotency factors, a delay in the initial induction of mesoderm specification, and a catastrophic disruption of the basic body plan. These data have revealed that Tcf7l1 is a novel negative regulator of pluripotency expressed in ESC and the embryo to facilitate the proper transition from self renewal to lineage specification during development. Importantly, my research takes a major step towards consolidating the understanding of the in vitro regulation of pluripotency with the actual function of the pluripotency GRN in vivo. I will also detail my work in developing a novel microfluidic device for in vitro culture of mouse embryos. Finally, I will discuss my engineering of a novel transgenic mouse model for inducible expression of the pluripotency factor Nanog and the discovery of its potential as a model for hepatocellular carcinoma.en_US
dc.language.isoenen_US
dc.rightsen_US
dc.rightsCopyright 2012 Jackson A. Hoffmanen_US
dc.subjectPluripotencyen_US
dc.subjectPrimitive Streaken_US
dc.subjectTcf7l1en_US
dc.subjectEpiblasten_US
dc.subjectMesodermen_US
dc.subjectEmbryonic Stem Cellsen_US
dc.subjectEpiblast Stem Cellsen_US
dc.subjectPrimingen_US
dc.subjectNanogen_US
dc.subjectSox2en_US
dc.subjectOct4en_US
dc.subjectBrachyuryen_US
dc.subjectMixl1en_US
dc.subjectMicrofluidicen_US
dc.subjectEmbryo Cultureen_US
dc.subjectHepatocellular Carcinomaen_US
dc.titleRegulation of the State of Pluripotency is Critical for Lineage Specification and Embryonic Developmenten_US
thesis.degree.departmentBiochemistry and Molecular Geneticsen_US
thesis.degree.disciplineBiochemistry and Molecular Geneticsen_US
thesis.degree.grantorUniversity of Illinois at Chicagoen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhD, Doctor of Philosophyen_US
dc.type.genrethesisen_US
dc.contributor.committeeMemberFrolov, Maximen_US
dc.contributor.committeeMemberLau, Lesteren_US
dc.contributor.committeeMemberTyner, Angelaen_US
dc.contributor.committeeMemberSchmidt, Jenniferen_US
dc.type.materialtexten_US


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