Date of Award
Doctor of Philosophy (PhD)
Tissue stem cells balance fate decisions of self-renewal and differentiation to maintain homeostasis over the lifetime of an organism, as well as to repair tissues upon injury and wounding. Disrupting the balance between self-renewal and differentiation results in pathology: excessive self-renewal at the expense of differentiation is associated with tumor initiation, whereas failure to properly self-renew leads to stem cell exhaustion and aging. Stem cell fate is under tight regulation by the surrounding microenvironment, or niche, which includes neighboring cell types, signaling molecules, extracellular matrix, and nutrients. While the role of stromal cells and the signals they produce has been extensively studied with regards to control of stem cell fate, relatively little known is about how tissue stem cells integrate extracellular nutrient availability with fate decisions. Moreover, while intracellular metabolic pathways have been shown to regulate the balance of self-renewal and differentiation, it remains unknown whether or not endogenous metabolic pathways or nutrient availability predispose stem cells towards transformation or control their responses to tissue injury.
Baksh, Sanjeethan C., "Metabolic Coordination of Stem Cell Fate Controls Tumor Initiation and Tissue Repair" (2021). Student Theses and Dissertations. 606.