微小RNA在多能干细胞中的功能与机制研究

项目名称： 微小RNA在多能干细胞中的功能与机制研究

项目编号： No.31471222

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 汪阳明

作者单位： 北京大学

项目金额： 100万元

中文摘要： 多能干细胞（包括胚胎干细胞、诱导多能干细胞等）为再生医学提供了最佳材质，但其最终能否被应用取决于我们对调控它们生物学性质的分子机制的理解。我们前期的研究证明了微小RNA是胚胎干细胞中的重要调控因子，并发现了调控胚胎干细胞增殖、细胞周期和自我更新的微小RNA家族(ESCC miRNAs)；然而是否还有其它调控胚胎干细胞自我更新的微小RNA以及ESCC miRNAs的作用机制仍然不清楚。本项目将针对这些问题展开深入研究。这些研究将发掘新的维持多能干细胞自我更新的微小RNA分子和家族，以及从新的角度，即miRNA与其它RNA相关调控路径（RNA可变剪切和长非编码RNA）之间的联系，来解析miRNA调控胚胎干细胞自我更新和分化的分子机制。本研究不仅对于理解miRNA调控机理的基础生物学有重要意义，也将为控制多能干细胞的自我更新和分化提供新的靶标分子和理论基础。

中文关键词： 微小RNA；RNA剪切；长非编码RNA；多能干细胞；自我更新

英文摘要： Pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)hold great potential for regenerative medicine. However, the molecular mechanisms underlying their self-renewal and differentiation are not yet fully understood, which prevents their use in regenerative medicine due to safety issues. Our previous results showed that miRNAs are important regulators of the self-renewal and differentiation of ESCs, and identified a cluster of miRNAs, ESCC miRNAs (Embryonic Stem cell Cell Cycle regulating miRNAs), that control proliferation, cell cycle progression and self-renewal of ESCs.Whether there are other miRNAs playing similar roles as ESCC miRNAs in supporting self-renewal, and how ESCC miRNAs function remain unanswered. We propose to identify novel miRNAs other than ESCC miRNAs that control ESC self-renewal. Furthermore, we propose to understand the molecular mechanisms underlying ESCC miRNAs'function from novel angles, that are based on the interaction between miRNAs and other RNA regulation pathways including alternative RNA splicing and long noncoding RNAs.The proposed study will advance our basic understanding on how miRNAs function, and also provide insights on novel targets and mechanisms that control the self-renewal and differentiation of pluripotent stem cells.

英文关键词： miRNAs;RNA splicing;Long noncoding RNAs;Pluripotent stem cells;Self-renewal