A Skin microRNA Promotes Differentiation by Repressing 'Stemness'

Nature. 2008 Mar 13;452(7184):225-9. doi: 10.1038/nature06642. Epub 2008 Mar 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cell Cycle
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Epidermal Cells
  • Epidermis / metabolism
  • Gene Expression Regulation
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Skin / cytology*
  • Skin / metabolism*
  • Stem Cells / cytology*
  • Zebrafish / genetics

Substances

  • 3' Untranslated Regions
  • MicroRNAs