A skin microRNA promotes differentiation by repressing 'stemness'

• Published in: Nature Vol. 452; no. 7184; pp. 225 - 229
• Main Authors: Fuchs, Elaine, Yi, Rui, Poy, Matthew N, Stoffel, Markus
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-03-2008; Nature Publishing; Nature Publishing Group
• Subjects: 3' Untranslated Regions - genetics; Animals; Base Sequence; Biological and medical sciences; Cell Cycle; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell division; Cell physiology; Cell Proliferation; Cells; Cells, Cultured; Computational Biology; Epidermis - cytology; Epidermis - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humanities and Social Sciences; Humans; Keratinocytes - cytology; Keratinocytes - metabolism; letter; Mice; Mice, Knockout; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular and cellular biology; Molecules; multidisciplinary; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Skin; Skin - cytology; Skin - metabolism; Stem cells; Stem Cells - cytology; Tissues; Vertebrates; Zebrafish - genetics; Gene silencing; Vertebrata; Regulation(control); Mammalia; RNA interference; Mouse; Rodentia; Micro RNA; Homeostasis; Skin; Cell differentiation; Gene expression
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature06642

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.