MiR-181c介导的表观遗传调控对骨髓间充质干细胞成肝分化的影响及其机制研究

项目名称： MiR-181c介导的表观遗传调控对骨髓间充质干细胞成肝分化的影响及其机制研究

项目编号： No.31201110

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 王越

作者单位： 中国人民解放军第二军医大学

项目金额： 21万元

中文摘要： 骨髓间充质干细胞（BMSCs）在肝微环境下的成肝分化机制具有重要的研究意义，而microRNA介导的表观遗传调控在其中的作用尚未阐明。本项目组在前期研究中发现肝微环境中的脂多糖LPS通过激活Akt1促进BMSCs成肝分化，并且miR-181c在这一过程中显著上调表达，但是miR-181c对BMSCs成肝分化的影响和机制尚需深入研究。因此，本项目组拟通过人BMSCs体内外成肝分化模型，采用miR-181c过表达和干扰等策略验证miR-181c在BMSCs成肝分化过程中的作用，并通过对miR-181c上游的Akt1相关信号通路的分析、对CARM1、miR-23a簇前体等miR-181c下游靶基因的研究，探讨miR-181c参与BMSCs成肝分化调控的表观遗传学机制，以期阐明LPS影响下BMSCs成肝分化过程中的关键microRNA分子，并为BMSCs的基础和应用研究提供新的靶点和方向。

中文关键词： 干细胞；多能性干细胞；非编码RNA；发育；成肝分化

英文摘要： The hepatic differentiation mechanisms of bone marrow derived mesenchymal stem cells(BMSCs)are important for both the basic and clinical studies. However, whether microRNA-mediated epigenetic regulation contributes to the mechanism of BMSCs hepatic differetiation in vivo and in vitro remains undefined by far. And the studies on this field may be urgent for the clincial application of stem cells. In our previous study, gut-derived bacterial lipopolysaccharide（LPS）, which is an important component exsiting in the hepatic extracellualr enviroment, was found to faciliate the hepatic differentiation of BMSCs in vitro with the activation of Akt1 and upregulation of miR-181c. But the role of Akt1/miR-181c pathway and its related mechanism remains undefined. In our current proposal, we plan to prove that miR-181c-related-pathway regulates BMSCs heaptic differention in vitro and in vivo employing Akt1 inhibitor, miR-181c overexpressing and inhibiting lentivirus. To further investigate the regulatory mechanisms of Akt1/miR-181c in MSCs heaptic differention, we also plan to study the signal pathways involved in the miR-181c transcription regulation and the miR-181c-interacted target genes. This study may increase the knowledge about BMSCs differentiation in vivo by the influences of LPS and other components in the hepatic

英文关键词： Stem Cells；Pluripotent Stem Cells；Non-coding RNAs；Development；Hepatic Differentiation