Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Nat Cell Biol. 2013 Oct;15(10):1153-63. doi: 10.1038/ncb2827. Epub 2013 Aug 25.
Skin stem cells (SCs) are specified and rapidly expanded to fuel body growth during early development. However, the molecular mechanisms that govern the amplification of skin SCs remain unclear. Here we report an essential role for miR-205, one of the most highly expressed microRNAs in skin SCs, in promoting neonatal expansion of these cells. Unlike most mammalian miRNAs, genetic deletion of miR-205 causes neonatal lethality with severely compromised epidermal and hair follicle growth. In the miR-205 knockout skin SCs, phospho-Akt is significantly downregulated, and the SCs prematurely exit the cell cycle. In the hair follicle, this accelerates the transition of the neonatal SCs towards quiescence. We identify multiple miR-205-targeted negative regulators of PI(3)K signalling that mediate the repression of phospho-Akt and restrict the proliferation of SCs. Our findings reveal an essential role for miR-205 in maintaining the expansion of skin SCs by antagonizing negative regulators of PI(3)K signalling.
皮肤干细胞（SCs）在早期发育过程中被特化并迅速扩增，为身体生长提供动力。然而，调控皮肤SCs 扩增的分子机制尚不清楚。在这里，我们报告了 miR-205 的一个关键作用，miR-205 是皮肤SCs 中表达最丰富的 microRNA 之一，它在促进这些细胞的新生扩增中发挥作用。与大多数哺乳动物的 miRNA 不同，miR-205 的基因缺失会导致新生鼠致死，并严重损害表皮和毛囊的生长。在 miR-205 敲除的皮肤SCs 中，磷酸化-Akt 显著下调，SCs 提前退出细胞周期。在毛囊中，这加速了新生SCs 向静止状态的转变。我们鉴定了多个 miR-205 靶向的 PI(3)K 信号负调控因子，它们介导磷酸化-Akt 的抑制，并限制SCs 的增殖。我们的研究结果揭示了 miR-205 通过拮抗 PI(3)K 信号的负调控因子，在维持皮肤SCs 扩增中的重要作用。
