Bend5调控胚胎干细胞分化为原始生殖细胞的分子机制研究

As a special cell population, primordial germ cell (PGC) is necessary for the continuation and evolution of species and occupies an irreplaceable position in the life cycle. PGC development is regulated by many micro-environmental factors and genes in the gonads, which makes it difficult to study the regulatory mechanisms in vivo. Using the system of inducing embryonic stem cells (ESCs) differentiation into PGC, we can study the molecular mechanism of key genes in PGC development in vitro. The BEN family proteins mediate protein-DNA and protein-protein interactions during chromatin organization and gene transcription. Our preliminary results showed that Bend5 is specifically overexpressed in the PGC, and overexpression Bend5 in ESC significantly improves the efficiency of ESC differentiation into PGC. Bend5 knockout affected PGC differentiation in vivo also. Bend5 may regulate the dynamic changes in gene transcription and chromatin modification through interacting with Oct4 and Tet1. We will utilize stem cell techniques, biochemical techniques and gene knockout mouse model to investigate the role of Bend5 in promoting ESC differentiate into PGC. Our findings will reveal a novel role of Bend5 in reproductive development process, answer basic scientific questions in reproductive development, and provide some important data for the clinical application of stem cells in the future.

原始生殖细胞（PGC）是物种延续及进化所必需的特殊细胞群，在生命循环中占有无可替代的地位。PGC的发育受许多微环境因素的影响和内源关键基因的调控，导致很难在体内研究其发育调控机制。利用体外诱导胚胎干细胞（ESC）分化为PGC的体系可以研究关键基因对PGC发育的调控机制。BEN结构域家族蛋白有介导蛋白-DNA和蛋白-蛋白互作的功能，能调节染色质结构和基因转录。申请人前期研究结果显示Bend5在PGC高表达，过表达Bend5能显著地提高ESC分化为PGC的效率；Bend5的敲除影响PGC在体内的发育；Bend5可能通过与Oct4和Tet1蛋白互作，从而调控基因转录和染色质的动态变化。项目将通过细胞和生化技术及基因敲除小鼠模型来全面挖掘Bend5调控ESC分化为PGC的分子机制，研究结果将揭示Bend5在生殖发育过程中的新功能，解答生殖发育的基本科学问题，为干细胞分化的应用提供重要的研究基础。

原始生殖细胞（PGC）是物种延续及进化所必需的特殊细胞群，在生命循环中占有无可替代的地位。PGC的发育受许多微环境因素的影响和内源关键基因的调控，导致很难在体内研究其发育调控机制。利用体外诱导胚胎干细胞（ESC）分化为PGC的体系可以研究关键基因对PGC发育的调控机制。BEN结构域家族蛋白有介导蛋白-DNA和蛋白-蛋白互作的功能，能调节染色质结构和基因转录。申请人研究结果显示Bend5在PGC高表达，过表达Bend5能显著地提高ESC分化为PGC的效率；Bend5的敲除影响PGC在体内的发育；Bend5通过与Oct4和Tet1蛋白互作，从而调控基因转录和染色质的动态变化。项目通过细胞和生化技术及基因敲除小鼠模型来全面挖掘Bend5调控ESC分化为PGC的分子机制，研究结果揭示Bend5在生殖发育过程中的新功能，解答生殖发育的基本科学问题，为干细胞分化的应用提供重要的研究基础。