Determinating the role of miRNA in myogenic progenitor maintenance and differentiation

这个申请是为了支持我关于肌肉祖细胞分化的细胞机制的研究项目。许多胚胎发育事件，包括干细胞和祖细胞的维持，都是通过小的非翻译RNA分子（称为mirna）的表达进行转录后调节的。然而，我们对miRNA如何促进个体组织的维持和分化知之甚少。我的实验室已经对Ars2进行了表征，我们和其他人已经证明它对miRNA的生物发生至关重要。通过体外C2C12细胞培养分化模型，我的实验室已经证明Ars2对于肌源性祖细胞自我更新的沉默是必要的，并且缺乏Ars2的肌源性细胞缺乏成熟的miRNA。此外，我们已经确定了Ars2功能的潜在调节因子RNPS1，它将Ars2隔离在成肌细胞的细胞质中，直到分化开始。

This application is to support my research program on the cellular mechanisms controlling differentiation of muscle progenitor cells. Many embryonic developmental events, including maintenance of stem and progenitor cells, are regulated post-transcriptionally through expression of small non-translated RNA molecules, called miRNAs. However, we know very little about how miRNA contribute to the maintenance and differentiation of individual tissues. My lab has characterized Ars2, and we and others have shown that it is essential for miRNA biogenesis. Using an in vitro C2C12 cell culture model of differentiation, my lab has shown that Ars2 is necessary for the silencing of self renewal in myogenic progenitor cells, and that myogenic cells deficient for Ars2 are deficient in mature miRNA. In addition, we have identified potential regulator of Ars2 function, called RNPS1, which sequesters Ars2 in the cytoplasm of myoblasts until initiation of differentiation.