精原细胞向生殖干细胞和生殖细胞转化的机制研究

Mechanism for Transdifferentiation of Spermatogonia into Germline Stem Cells and Germ Cells

生殖干细胞是生殖细胞发育的早期阶段。生殖干细胞是一类特殊类型的成体干细胞,它不但具有干细胞的特性,还具有传递遗传信息的能力。本项目以阐明精原干细胞转换体系为中心,以研究精原干细胞向雌性生殖干细胞转换的机制为主线,揭示其复杂机制和探索其在性分化异常相关疾病机理研究中的应用。基于这一主线,我们首先根据前期研究结果建立了精原干细胞向雌性生殖干细胞体外转化体系,根据这一结果和技术平台以及前期研究已建立的体内转换小鼠模型,从表观遗传学、细胞代谢和细胞器重塑等角度揭示了精原干细胞向雌性生殖干细胞转化的机制。另一方面,利用已建立的体内转换小鼠模型和已建立的性分化异常疾病资源库和家系库等揭示了性分化异常及相关疾病发生机制。项目的实施为性分化异常相关疾病的防治提供理论依据和技术平台,为人类优生和出生缺陷的防治奠定基础。

Germline stem cells are early stage of germ cells development. Germline stem cells are a special type of adult stem cells that not only have the characteristics of stem cells but also have the ability to deliver genetic information.This project focuses on the mechanism for transdifferentiation of spermatogonia stem cells into female germline stem cell,revealing its complex mechanism and exploring its application in the study of sex differentiation abnormalities related diseases. Based on this main line,we first established the in vitro system for transdifferentiation of spermatogonia stem cell intofemale germline stem cell. Based on this result and technique platform as well as the mouse model that derived from previous study,we revealed the mechanism for transdifferentiation of spermatogonia stem cells into female germline stem cell from the perspective of epigenetics,cell metabolism and organelles reshape. On the other hand,the project revealed the mechanism of sex differentiation abnormalities and its related diseases according to the mouse model that derived from in vivo transdifferentiation system and the resource library of sex differentiation abnormalities related diseases. This project provides the theoretical basis and technology platform for the diagnosis and treatment of sex differentiation abnormalities related diseases,and provides the foundation of human eugenics and prevention of birth defects.