Yang, Y; (2015) Functions of SoxE in direct conversion of mouse embryonic fibroblasts (MEFs) to neurons and neural stem cell (NSC) maintenance. Doctoral thesis , UCL (University College London).

Text Yuan Yang Thesis Y Yang[1].pdf Download (43MB)

Abstract

Proneural transcriptional factor Ascl1 plays essential roles in inducing neuronal differentiation and subtype specification in developing central nerve system. More recently, Ascl1 has been identified as one of the critical factors that are involved in direct reprogramming of fibroblasts to functional neurons. As Ascl1 is essential to activate neuronal specific programme in both neuronal differentiation and direct reprogramming, we hypothesis that identifying common Ascl1 downstream genes allows us to understand molecular mechanisms in both programmes. In this study, genome-wide expression microarrays indicated that Sox8 was involved in both Ascl1-medicate reprogramming and neural stem cell maintenance in vitro. Both Sox8 Gain-of-Function and Loss-of-Function reduced the generation of induced neurons suggested the possibility that Sox8 was transiently expressed during the reprogramming process. Furthermore, ectopic expression of Sox8 or Sox9 inhibited Ascl1-induced neuronal differentiation of neural stem cells in vitro. Sox8 or/and Sox9 Loss-of-Function significantly reduced neural stem cell proliferation in vitro. The observation was also confirmed by genome-wide expression microarray experiments, which identified a number of cell cycle related genes were deregulated by Sox8 or/and Sox9. These data suggested that SoxE (specifically Sox8 and Sox9) activities were essential to maintain neural stem cell proliferation in vitro.

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