研究生殖干细胞的增殖和分化是解决生殖器官功能下降和衰老的关键手段。近年来，出生后雌性哺乳动物生殖干细胞（FGSC）的分离鉴定和调控成为研究热点，然而其具体调控机制尚未明确。现有报道表明，对多种干细胞增殖、分化起重要调控作用的Hedgehog通路，也调控着果蝇生殖干细胞的增殖和分化。我们在证实FGSC存在的基础上，发现此通路同时存在于小鼠FGSC中，故推测Hedgehog通路可能是调控哺乳动物FGSC增殖和分化的关键通路。本项目拟通过分析Hedgehog通路在FGSC增殖和分化中作用；通过Hedgehog通路关键转录因子Gli1高表达载体/Gli1-shRNA载体介导此通路活性在FGSC高/低表达后，将此FGSC移植到不孕模型小鼠卵巢中，观察卵泡形成发育及产仔影响；通过卵巢内微注射Gli1高表达载体/Gli1-shRNA进一步观察对不孕模型小鼠卵巢功能恢复的影响,为卵巢功能重塑提供实验依据。

The proliferation and differentiation of germ stem cells is a key methods to solve functional decline and aging of the reproductive organs. In recent years, it is become a hotspot for the isolation、identification and regulation of female germline stem cell(FGSC) after the birth in mammals, however, the specific regulatory mechanism of FGSC is unknown.It is proved that Hedgehog(Hh) pathway regulated the proliferation and differentiation of fruit fly FGSC as well as other stem cells. After confirmed the exist of FGSC, we found there is a Hh pathway in mice FGSC which maybe plays a key role for FGSC in mammals. We will propose to analyze the role of Hh pathway in the proliferation and differentiation of FGSC;at first, we will construct lentivirus overexpress/shRNA vector of the key transcription factor Gli1 of Hh pathway and transfer the lentivirus vectors to FGSC, and construct FGSC stable cell line by G418, then observe the follicle development and pregnant after transplant FGSC stable line to mouse model of ovarian infertility;next we will explore the recovery of ovarian function by microinjecting the lentivirus vectors to ovarian infertility and provide experimental basis for remodeling ovarian function.