A skin microRNA promotes differentiation by repressing 'stemness'
A skin microRNA promotes differentiation by repressing 'stemness'
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DOI：
10.1038/nature06642
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发表时间：
2008-03-13
期刊：
影响因子：
64.8
通讯作者：
Fuchs, Elaine
中科院分区：
文献类型：
--
作者：
Yi, Rui;Poy, Matthew N.;Fuchs, Elaine
在分层上皮组织中，稳态依赖于位于最内层基底层内的干细胞的自我更新能力（1）。随着基底细胞变为基底上细胞，它们失去增殖潜力并开始终末分化程序（2，3）。在这里，我们发现microRNA- 203在皮肤中伴随着分层和分化而被诱导。通过改变体内miR- 203的时空表达，我们发现miR- 203通过限制增殖潜能和诱导细胞周期退出来促进表皮分化。我们确定p63是脊椎动物中miR- 203的保守靶点之一。值得注意的是，p63是复层上皮组织中干细胞维持的重要调节剂（4-9）。我们表明，miR- 203直接抑制p63的表达：当Dicer 1或miR- 203不存在时，它无法在基底上关闭，而当miR- 203过早表达时，它会在基底上受到抑制。我们的研究结果表明，miR- 203定义了增殖的基底祖细胞和终末分化的基底上细胞之间的分子边界，确保相邻层的正确身份。
In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer(1). As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme(2,3). Here, we show that microRNA- 203 is induced in the skin concomitantly with stratification and differentiation. By alteringmiR- 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(4-9). 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.