早期胚胎是机体发育的基石，胚胎干细胞（ESC）在疾病应用中前景广阔。对人ESC遗传物质稳定维持机制的研究可促进其走向安全应用，也有助于深入认识发育相关的疾病机理。申请人前期发现一个小鼠ESC特异表达的调控遗传物质稳定的多能因子Filia，调节DNA损伤反应的多个环节。缺失导致小鼠ESC遗传物质不稳定，致瘤能力显著增强。Filia在人类中的同源基因是ECAT1。二者的蛋白质序列保守性仅为36%，且结构域差异显著。本项目拟研究ECAT1在人ESC遗传物质稳定性维持中的功能及机制，并利用人ESC研究从原发性不孕症病人中筛选到的ECAT1突变体对胚胎发育的影响。结果有望为人多能干细胞安全应用和不孕症研究提供理论基础。

Early embryos are designated to develop into all cell types in the body. Embryonic stem cells (ESCs) have promising implication in cell-based therapy. Investigating the molecular basis governing the genomic integrity of ESCs is critical to address the tumorigenic challenges and to understand development related diseases. We previously identified Filia as a guardian of genome stability in mouse embryonic stem cells (mESCs). Filia is a regulator of DNA damage response. mESCs without Filia have robust genomic instability and undergo malignant transformation. ECAT1, the human homolog of mouse Filia, encode a protein sharing 36% identity of amino acid sequence with Filia. There are many different domains between Filia and ECAT1. This study is aimed to understand the roles of ECAT1 in human ESCs and to examine the functional abnormalities of various ECAT1 mutants identified in female patients with primary infertility.