dFmrp/miRNA途径介导生殖干细胞命运决定的分子机制研究

中文摘要

干细胞命运决定-即不对称分裂机制研究是干细胞领域的国际前沿热点课题。近年报道FMRP 参与干细胞的增殖和分化，但其具体的分子机制仍不清楚。我们实验室在前期研究中发现dFmrp 和miRNA 途径中的关键成分-dAGO1 蛋白，均参与生殖干细胞的命运决定，并且二者存在很强的生化和遗传作用，推测dFmrp 很可能潜在利用miRNA 途径调节生殖干细胞命运。本项目的主要目标是解析dFmrp 与miRNA 途径的相互作用在生殖干细胞命运决定中的功能重要性。具体采用免疫共沉淀、microRNA 芯片、genechips 芯片鉴定与dFmrp 相关的microRNAs 和mRNAs，并结合遗传学手段体内外检测dFmrp/miRNA 途径介导的翻译调节决定生殖干细胞命运的分子机制。此项目的实施不仅将使我们深入认识干细胞不对称分裂机制的复杂性，并且可能为临床上"癌症干细胞"的治疗提供新思路和新方案。

英文摘要

The elucidation of the regulatory mechanism that determines stem cell fate is the key.for understanding the fundamental role in development and tissue homeostasis. Previous.studies have demonstrated that FMRP (Fragile X mental retardation protein) plays an.essential role in regulating the self-renewal and differentiation of stem cell. However,.the molecular mechanism remains elusive. Our lab has reported that dFmrp and dAGO1.protein (a crucial component in miRNA pathway) regulate the fate of stem cell and they.exist strong genetic and biochemical interaction. These clues suggested that dFmrp might.use miRNA pathway to regulate the fate of stem cell. The goal of this proposal is to.further decipher the functional importance of the interaction between dFmrp and the.miRNA pathway in the fate of stem cell. The techniques of Co-IP, MicroRNA array,.Genechip will be applied to identify the microRNAs and mRNAs associated with dFmrp. The.mechanism of the fate determination of stem cell mediated by FMRP/miRNA pathway will be.elucidated by genetic means in vitro and in vivo. In addition, understanding the.complexity of molecular mechanism of asymmetric division of stem cell is important for.the development of therapeutic intervention for cancer stem cell in clinic.