全球约有15%的育龄夫妇面临生殖障碍问题。配子缺乏是导致不孕不育症发生的重要因素之一。利用干细胞技术产生功能配子是当前干细胞领域研究的热点课题。利用iPSC技术和生殖细胞分化技术获得功能配子已经取得成功，但通过转分化技术将体细胞转分化为生殖细胞目前仍未见报道。本项目拟通过阶段性的过表达多能性因子组合或采用小分子化合物处理使体细胞转变为中间状态细胞，进而过表达Blimp1、Prdm14和Tfap2c等重要调控因子，获得原始生殖细胞样细胞。将原始生殖细胞样细胞移植到睾丸组织或卵巢组织，最终获得具有功能的精子和卵母细胞；或通过体外分化使雄性原始生殖细胞样细胞完成减数分裂并获得精子细胞。与iPSC技术相比，体细胞转分化获得功能细胞所需时间更短，步骤更简略，还可以回避iPSC技术所带来的安全性问题，因而具有一定的优势。本研究的开展将给不孕不育症的治疗提供配子来源，同时促进对生殖细胞发生机制的了解。

Around 15% couples suffering from infertility, while one of the main factors is the lack of qualified gametes. The great promise of artificial gametes by stem cell technology resides in their future application on reproductive treatments for all these people wishing to have genetically related children. Although generation of gametes by iPSC and germ cell differentiation have been succeed, however, transdifferentiation of germ cells from somatic cells is difficult. Here we hypothesis that obtain intermediate cells by transient overexpression of the pluripotent factors in somatic cells or treated with small compounds, then overexpress Blimp1, Prdm14, Tfap2c and Nanog in the intermediate cells to obtain primordial germ cells like cells. We may obtain functional sperms or oocytes by transplanting these primordial germ cells like cells into the testes or ovaries. Compared to iPSC reprogramming, transdifferentiation of somatic cell into functional germ cells is faster, easier and has fewer chance of tumor formation. This project will contribute to the generation of artificial spermatids for the treatment of infertility, and improve the mechanism study of the primordial germ cell specification.