부산대학교 도서관

Abstract: The involvement of microRNAs (miRNAs) in orchestrating self-renewal and differentiation of stem cells has been revealed in a number of recent studies. And while in human pluripotent stem cells, miRNAs have been directly linked to the core pluripotency network, including the cell cycle regulation and the maintenance of the self-renewing capacity, their role in the onset of differentiation in other contexts, such as determination of neural cell fate, remains poorly described. To bridge this gap, we used three model cell types to study miRNA expression patterns: human embryonic stem cells (hESCs), hESCs-derived self-renewing neural stem cells (NSCs), and differentiating NSCs. The comprehensive miRNA profiling presented here reveals novel sets of miRNAs differentially expressed during human neural cell fate determination in vitro. Furthermore, we report a miRNA expression profile of self-renewing human NSCs, which has been lacking to this date. Our data also indicates that miRNA clusters enriched in NSCs share the target-determining seed sequence with cell cycle regulatory miRNAs expressed in pluripotent hESCs. Lastly, our mechanistic experiments confirmed that cluster miR-17–92, one of the NSCs-enriched clusters, is directly transcriptionally regulated by transcription factor c-MYC.Graphical Abstract:
Highlights: Upon differentiation from hESCs, self-renewing neural stem cells maintain fast proliferation and stem cell-like cell cycle propertiesMiRNA sequencing reveals novel sets of differentially expressed miRNAs during neural cell fate determination in vitroMiRNA clusters enriched in NSCs share the seed sequence with cell cycle regulatory miRNAs in pluripotent hESCs and one of them, miR-17–92, is directly transcriptionally regulated by c-MYC