Shin-biology regulated by protein lifetime

Tissue stem cells are capable of self-renewal and multipotency to differentiate into multiple cell types and maintain tissue homeostasis by supplying new functional cells. Many adult tissue stem cells enter a quiescent state, the G0/G1 phase of the cell cycle, in which proliferation and differentiation stop. Stem cells dynamically alter their properties when they are reactivated from quiescence or differentiated into functional cells. At the same time, stem cells undergo large-scale remodeling in protein composition (proteome remodeling). This is accomplished by significant changes in the proteolytic system and protein lifespan; however, the underlying mechanisms that regulate these changes remain unclear. I have previously demonstrated lysosomal regulation of neural stem cell quiescence by proteolysis of membrane receptors in lysosomes; however, the overall molecular mechanism governing this lysosomal regulation also remains unknown. In this study, I will comprehensively analyze protein lifespan during neural stem cell quiescence, activation, and differentiation to elucidate the underlying mechanisms of proteome remodeling in response to functional and state changes in neural stem cells. I will also analyze the proteome change in neural stem cell dysfunction caused by aging and brain diseases to elucidate the molecular mechanisms that control their maintenance in the brain.

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