INSERM U861, I-Stem, AFM, Evry Cedex, France.
Dev Biol. 2011 Aug 15;356(2):506-15. doi: 10.1016/j.ydbio.2011.06.004. Epub 2011 Jun 12.
The molecular mechanisms controlling the differentiation of human basal keratinocyte stem cells towards the epidermis are well characterized, whereas the earliest process leading to the specification of embryonic stem cells into keratinocytes is still not well understood. MicroRNAs are regulators of many cellular events, but evidence for microRNA acting on the differentiation of human embryonic stem cells into a specific lineage has been elusive. By using our recent protocol for obtaining functional keratinocytes from hESC, we attempted to analyze the role of microRNAs in the early stages of epidermal differentiation. Thus, we identified a set of 5 microRNAs, namely miR-200a, miR-200b, miR-203, miR-205 and miR-429, that are specifically overexpressed during the early stages of the differentiation process. Interestingly, our functional analyses revealed an instrumental role of miR-203, which had been previously shown to play a key role during the formation of the pluristratified epidermis by basal keratinocyte stem cells, in the early keratinocyte commitment. These results highlight the determinant and unique role of miR-203 during the entire process of epidermal development by extending its spectrum of action from the early commitment of embryonic stem cells to ultimate differentiation of the organ.
控制人类基底角质细胞干细胞向表皮分化的分子机制已得到很好的描述，而导致胚胎干细胞特化为角质细胞的最早过程仍未得到很好的理解。 microRNAs 是许多细胞事件的调节剂，但 microRNA 作用于人类胚胎干细胞分化为特定谱系的证据一直难以捉摸。通过使用我们最近获得功能性角质细胞的方案，我们试图分析 microRNAs 在表皮分化早期阶段的作用。因此，我们鉴定了一组 5 个 microRNAs，即 miR-200a、miR-200b、miR-203、miR-205 和 miR-429，它们在分化过程的早期阶段特异性过表达。有趣的是，我们的功能分析揭示了 miR-203 的重要作用，先前的研究表明，miR-203 在基底角质细胞干细胞形成多分层表皮的过程中起着关键作用，在早期角质细胞定向分化中起着重要作用。这些结果突出了 miR-203 在整个表皮发育过程中的决定和独特作用，将其作用范围从胚胎干细胞的早期定向延伸到器官的最终分化。
