驱动蛋白Oocyte-G1对生殖细胞发育的作用及其机制

The normal development of germ cells is critical for human reproduction.This project aims at studying regulatory mechanism of germ cell development, especially germline stem cell development. Based on the our previous research, we employ in vivo and in vitro transgeneic technology, condictional gene knockout, RNA interference (RNAi), ChIP-chip or ChIP-seq to undertake the research as follow: 1) the regulatory effects of Oocyte-G1 on proliferation or apoptosis of germline stem cells; 2) the regulatory effects of Oocyte-G1 on differentiation of germline stem cells; 3)the regulatory effects of Oocyte-G1 on proliferation, differentiation and apoptosis of germ cells; 4) mechanism of action and regulatory networks of Oocyte-G1 on germ cell development. This project will promote the understanding of mechanism on human reproduction, particularly it has great significance for deep understanding of human gametogenesis. This project will also provide theoretical bases and lay the foundation for treatment of human infertility and development of contraceptives and have important roles in population regulation, human eugenics and animal reproduction. Besides, this project will provide references for functional study of other kinesin protein.

生殖细胞的正常发育是确保人类生殖的关键。本项目针对生殖细胞特别是生殖干细胞的发育调控机理,结合项目组的研究基础和前期工作并利用体内外转基因、条件性基因敲除、免疫共沉淀和RNA干扰技术以及ChIP-chip或ChIP-seq技术等进行下列研究: 1)Oocyte-G1对生殖干细胞增殖或凋亡的调控作用; 2)Oocyte-G1对生殖干细胞分化的调控作用; 3)Oocyte-G1对生殖细胞增殖、分化与凋亡的调控作用; 4)Oocyte-G1对生殖细胞发育的作用机制和调控网络。通过本项目研究能进一步理解人类生殖机制，特别是对人类配子发生的深入理解具有重要意义。同时为人类不育症的治疗以及为避孕药物的研发提供理论依据和奠定基础。对人口调控、优生、动物繁殖起重要作用。也为研究其它驱动蛋白功能提供参考。

生殖细胞的正常发育是确保人类生殖的关键。通过项目实施, 建立了小鼠, 大鼠, 人雌性生殖干细胞分离纯化, 体外培养与体内外分化系统, 并建立相应的细胞系及特征化其功能; 建立了小鼠精原干细胞或雄性生殖细胞体外发育与调控系统; 发现雌性生殖干细胞具有与精原干细胞相似的形态, 生长方式, 生物学特性以及基因表达与非编码RNA谱等。 阐明了新颖驱动蛋白因子Oocyte-G1具有促进生殖细胞凋亡的作用并通过激活Caspase-3信号通路实现其调节作用，发现Caspase-3是其相互作用的蛋白因子。发表SCI论文15篇，其中影响因子大于5论文7篇。培养博士研究生8名，硕士研究生4名，获上海市优秀博士论文奖1人。上述结果对进一步理解人类生殖机制，特别是对人类配子发生的深入理解具有重要意义。同时为人类不育症的治疗以及为避孕药物的研发提供理论依据和奠定基础。对人口调控、优生、动物繁殖起重要作用并为研究其它驱动蛋白功能提供参考。