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The Role of the GSK3 Inhibition-Tcf7l1 Axis in Facilitating Exit from Naive Pluripotency

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thesis
posted on 06.08.2019, 00:00 by Yu Zhang
This thesis dissertation examines events which allow embryonic stem cells (ESC) to progress from early or “naïve” pluripotency, a state characterized by propensity for self-renewal, to late or “primed” pluripotency, whence ESC become competent to divide into lineage-specifying cells. This work occurs in two sections. The first section examines the role of the GSK3i-Tcf/Lef axis in the exit from naïve pluripotency. The second section elucidates an epigenetic mechanism by which Tcf7l1 drives exit from naïve pluripotency. Based on conclusions from this work, I propose that Tcf7l1-mediated enhancer decommissioning accommodates the need for pluripotent cells to rapidly alter their response to differentiation signals in the progression towards gastrulation, a likely mechanism by which Wnt/β-catenin signaling controls other stem cell lineage decisions.

History

Advisor

Merrill, Brad

Chair

Merrill, Brad

Department

Biochemistry and Molecular Genetics

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Benevolenskaya, Elizaveta Frolov, Max Lau, Lester Rehman, Jalees Raychaudhuri, Pradip Tyner, Angela

Submitted date

May 2019

Issue date

28/05/2019

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