TGF-β调控的LncRNAs在胚胎干细胞中功能及机制的研究

项目名称： TGF-β调控的LncRNAs在胚胎干细胞中功能及机制的研究

项目编号： No.91540108

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： 郗乔然

作者单位： 清华大学

项目金额： 85万元

中文摘要： 长链非编码RNA(LncRNAs)在细胞发育和分化过程中有非常重要的作用。LncRNAs的一个主要功能就是通过结合染色质调控蛋白比如染色质修饰蛋白和重塑蛋白在表观遗传水平上调节基因的表达。我们过去的工作表明在小鼠胚胎干细胞分化中TGF-β信号通路和表观遗传图谱有相互作用。也就是说，被调控基因的表观遗传图谱决定了它对TGF-β信号通路如何反应。但是，什么因子介导TGF-β信号通路和表观遗传图谱的相互作用以及这个因子是LncRNAs的可能性的相关研究几乎为空白。我们的初步研究表明TGF-β特异性调控的LncRNAs存在于小鼠胚胎干细胞和早期分化的干细胞中。我们的研究将致力于诠释TGF-β调控的LncRNAs如何在胚胎发育过程中发挥作用，以及这些LncRNAs调控目标基因表达的机制。

中文关键词： 胚胎干细胞；长链非编码RNA；表观遗传学；TGF-β信号转导；转录调控

英文摘要： Long non-coding RNAs (LncRNAs) have been found to play important roles in cell development and differentiation. A major function of LncRNAs is to facilitate epigenetic regulation of gene expression by coupling with chromatin regulators such as chromatin modifiers and remodelers. Our previous work has suggested a crosstalk between TGF-β signaling pathway and the epigenome during murine embryonic stem cell differentiation. Thus, the epigenetic landscape of target genes determines how they, in a cell context-dependent manner, respond to TGF-β signaling. But what mediates the crosstalk between TGF-β signaling and the epigenome, and could LncRNAs play such a role are not known. In this proposal, I describe our preliminary data on identification of a subset of LncRNAs whose expression are TGF-β dependent during murine embryonic stem cell differentiation. And I propose to further investigate the roles of these LncRNAs in TGF-β responses during embryonic development, and decipher the molecular mechanism by which these LncRNAs regulate expression of target genes.

英文关键词： embryonic stem cell;LncRNAs;epigenetics;TGF-β signaling ;transcription regulation