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Publication : A skin microRNA promotes differentiation by repressing 'stemness'.

First Author  Yi R Year  2008
Journal  Nature Volume  452
Issue  7184 Pages  225-9
PubMed ID  18311128 Mgi Jnum  J:170443
Mgi Id  MGI:4946489 Doi  10.1038/nature06642
Citation  Yi R, et al. (2008) A skin microRNA promotes differentiation by repressing 'stemness'. Nature 452(7184):225-9
abstractText  In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer. As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme. Here, we show that microRNA-203 is induced in the skin concomitantly with stratification and differentiation. By altering miR-203's spatiotemporal expression in vivo, we show that miR-203 promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit. We identify p63 as one of the conserved targets of miR-203 across vertebrates. Notably, p63 is an essential regulator of stem-cell maintenance in stratified epithelial tissues. We show that miR-203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR-203 is absent and it becomes repressed basally when miR-203 is prematurely expressed. Our findings suggest that miR-203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.
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