Characterization of nuclear segregation of RNA as a potential novel marker and regulation mechanism of quiescence in neural stem cell

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Characterization of quiescent stem cells is a crucial step in manipulating quiescence in tissue regeneration and repair, and cancer treatment. Through the characterization of a Drosophila melanogaster mutant, I uncovered a potential novel regulation mechanism of neural stem cell quiescence. I observed that downregulation of Nucleoporins and karyopherins induces quiescence in Drosophila melanogaster neural stem cells. Nucleocytoplasmic transport components appeared altered in vivo in Drosophila neural stem cell and in vitro in a cell culture model of mouse adult hippocampal neural stem cell. I thus hypothesized that transport of particular cargo should be altered in quiescent neural stem cells, and demonstrated that polyadenylated RNA is segregated to the nucleus in quiescent neural stem cells in both models. I also started to characterize targets linked to this segregation mechanism, and showed that nuclear segregation of polyadenylated RNA occurred in mouse muscle satellite cells. Although much characterization of this novel mechanism in stem cell quiescence still has to be done, I offer a view of a potential novel regulator as well as a potential novel marker of quiescence.
Date of Award27 Jun 2019
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorRita Sousa-Nunes (Supervisor)

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