卵泡颗粒细胞与卵母细胞互作,维持了卵母细胞的生长发育。CXXC锌指蛋白1（CFP1）介导的组蛋白3赖氨酸4（H3K4）的甲基化在CpG岛基因启动子区域聚集，促进组织特异基因的转录。这种表观遗传修饰对哺乳动物发育至关重要。但是CFP1在颗粒细胞中的作用，及其通过颗粒细胞影响卵母细胞生长发育的具体功能还不清楚。我们的初步实验表明，缺失CFP1导致了小鼠颗粒细胞增殖障碍、次级卵泡发育受阻、卵母细胞凋亡，最终导致雌性不育。本项目将利用体内和体外卵巢培养模型，结合单细胞转录组测序，筛选CFP1影响颗粒细胞增殖的关键分子；同时分析CFP1通过颗粒细胞影响卵母细胞生长发育的分子机理，最终确定CFP1介导的组蛋白H3K4甲基化修饰在卵泡发育中的作用及分子机理，进一步完善颗粒细胞与卵母细胞互作促进卵母细胞生长发育机理，为临床研究和应用奠定基础。

The follicular granulosa cells interact with the oocyte to maintain the growth and development of the oocyte. CXXC zinc finger protein 1 (CFP1)-mediated methylation of histone 3 lysine 4 (H3K4) accumulates in the promoter region of the CpG island gene, promoting transcription of tissue-specific genes. This epigenetic modification is critical for mammalian development. However, the role of CFP1 in granulosa cells and its specific function of affecting the growth and development of oocytes by granulosa cells are unclear. Our preliminary experiments showed that the deletion of CFP1 led to granulosa cell proliferation disorder, the block of secondary follicular development, and oocyte apoptosis, which eventually led to female sterility. This project will use in vivo and in vitro ovarian culture models, combined with single-cell transcription sequencing, to screen for key molecules that affect the proliferation of granulosa cells by CFP1. Simultaneously we analyze the molecular mechanism of CFP1 affecting oocyte growth and development through granulosa cells, and finally determine CFP1-mediated the role of H3K4 methylation modification in follicular development and molecular mechanism. This will further understand the interaction between granulosa cells and oocytes to promote the growth and development of oocytes, and lay a foundation for clinical research and application.