A skin microRNA promotes differentiation by repressing ‘stemness’

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.

Regulation of lung endoderm progenitor cell behavior by miR302/367

“…1243 RESEARCH ARTICLE miR302/367 and lung endoderm development Little is known about the ability of miRNAs to regulate tissuespecific progenitor populations. In the skin, miR203 promotes differentiation of skin basal progenitor cells by repressing the important skin progenitor maintenance factor p63 (Lena et al, 2008;Yi et al, 2008;Wei et al, 2010). However, less is known in the lung.…”

Attributes of adult stem cells

“…Stem cells, yellow; TACS, blue. DP, dermal papilla; Dpp, decapentaplegic; IRS, inner root sheath; ORS, outer root sheath; TA, transit amplifying compartment; TD, terminally differentiation; Upd, unpaired cycle exit and promotes differentiation in the epidermis, and K14-miR-203 transgenic mice are depleted of basal stem cells [39].…”

p53/p63/p73 in the Epidermis in Health and Disease

“…Furthermore, p63 directly inhibits expression of miR-138, miR-181a/b, and miR130b in primary human keratinocytes (Rivetti di Val Cervo et al 2012). In turn, p63 expression in epidermal keratinocytes is regulated by miR-203, miR-720, and miR-574-3p, which are expressed in cells within the suprabasal epidermal layer and restrict p63 expression to basal cells (Yi et al 2008;Chikh et al 2011). In addition to the hair bulb, epidermal progenitors generate the sebaceous gland, which secretes sebum via the duct penetrating the upper part of the follicular epithelium and extrudes it into the hair follicle infundibulum (Niemann and Horsley 2012).…”