干细胞分化配子是生殖发育研究领域的难点和热点。胚胎干细胞和诱导多能性干细胞在临床应用上由于材料来源、致瘤性、伦理和免疫排斥等问题限制了其应用。相比较而言，皮肤毛囊结构中的干细胞却是一种非常有前景的向配子分化的干细胞类型。为了筛选适宜向配子分化的干细胞，并探索干细胞向卵母细胞分化的诱导机制，本项目拟分析皮肤毛囊不同Niche来源干细胞向生殖细胞分化的差异，甄选较适宜Niche的干细胞用于诱导分化，以期获得高质量的原始生殖细胞；探讨毛囊干细胞向原始生殖细胞分化中外胚层细胞形成的必要性，阐述体外形成的原始生殖细胞的特化过程及其表观调节机制；分析体外来源的原始生殖细胞向卵母细胞分化中减数分裂启动的诱导调控机制，借助体内异位发育促进功能卵子的获得。本项目拟解决的关键科学问题在理论上将丰富我们对早期配子发生机制的认识；在实践中，毛囊干细胞分化卵母细胞可能会为今后的不孕不育治疗提供一种新的策略和途径。

Gamete differentiation from stem cells is a difficult but attractive topic in the field of reproduction and development. The use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is limited in clinical application due to their material sources, tumorigenicity, ethics and immune rejection. In comparison, adult stem cells within hair follicles are promising stem cell resources for gamete differentiation. To select the suitable stem cells for gamete differentiation and elucidate the mechanisms of oocyte differentiation, this program aims to analyze the differences of germ cell differentiation from skin hair follicle stem cells derived from different niches, and select the suitable niche stem cells for gamete differentiation, in order to obtain high quality of primordial germ cells. At the meantime, we will investigate the necessity of epiblast-like cells (EpiLCs) formation during differentiation from hair follicle stem cells to primordial germ cells, and elucidate the specialized process of primordial germ cell formation in vitro including the regulatory mechanisms of epigenetic modifications. Furthermore, this program will demonstrate the mechanisms underlying meiosis initiation during oocyte differentiation from in vitro derived primordial germ cells, and promote the acquisition of functional eggs via in vivo ectopic development. The scientific issues involved in this project will theoretically enrich our knowledge on early gametogenesis. In practice, oocyte differentiation from hair follicle stem cells may provide a new strategy for future treatment of infertility.