长非编码RNA调控肌肉干细胞增殖和分化的分子机制研究

项目名称： 长非编码RNA调控肌肉干细胞增殖和分化的分子机制研究

项目编号： No.91540104

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 程红

作者单位： 中国科学院上海生命科学研究院

项目金额： 80万元

中文摘要： 数目和种类繁多的长非编码RNA（lncRNA）可以通过各种不同机制调控细胞分化、个体发育等重要生命过程。目前对lncRNA的认识还仅是冰山一角，新的lncRNAs及lncRNA的新的作用机制正在不断被发现。lncRNA在骨骼肌分化过程中扮演重要角色。然而，截至目前，多数研究是在成肌细胞系中进行的，可能不能够完全忠实再现lncRNAs在体内如何调控肌肉干细胞的功能。本项目利用最新建立的原代小鼠骨骼肌干细胞的体外扩增和分化系统，通过高通量测序，鉴定了近20种在肌肉干细胞的增殖和分化中显著差异表达的lncRNAs。初步功能实验已经发现了其中两个lncRNA在肌肉干细胞分化中起重要调控作用。我们计划继续系统研究这些lncRNAs在肌肉干细胞增殖和分化过程中的功能，重点揭示其发挥调控功能的分子机制和自身代谢规律。

中文关键词： 长非编码RNAs；肌肉干细胞；增殖和分化；分子机制；代谢规律

英文摘要： Although discovered relatively recently, lncRNAs are considered the most numerous and functionally diverse class of RNAs. New lncRNAs and new functioning mechanisms of lncRNAs have been continuously identified. Multiple studies indicate that lncRNAs are critical players in regulating muscle stem cell differentiation. However, most of these studies were carried out in myoblast cell lines that might not faithfully reflect the actual roles of lncRNAs in vivo. Here, using the recently developed muclsle stem cells in vitro expansion and differentiation system, we identified ~20 lncRNAs whose expression significantly changed during differentiation. We plan to systematically examine the roles of these lncRNAs in muscle stem cell proliferation and differentiation. For those that have important roles, we plan to thoroughly investigate the molecular mechanism and metabolism of the lncRNAs thenselves. This project will not only advance our understanding for muscle regeneration, more importantly, will help us comprehend lncRNA metabolism and possibly reveal novel mechanism for lncRNA function.

英文关键词： lncRNAs;muscle stem cell;proliferation and differentiation;molecular mechanism;metabolism