基于单细胞多组学技术研究人类胚胎生殖细胞命运转变的调控机制

生殖系发育的异常与反复流产、胚胎停育密切相关。胚胎生殖细胞是胚胎时期遗传信息的载体，其正常分化发育是遗传信息代际间传递的重要基础。我们在前期的工作中初步明确了人类胚胎生殖细胞（hFGCs）的基因表达调控规律，但hFGCs时空发育的表观遗传调控机制，仍不完全清楚。本项目拟基于单细胞多组学技术（scCOOL-seq），系统研究不同胚胎周数、不同发育阶段hFGCs的DNA甲基化和染色质开放状态动态的变化特征，揭示调控hFGCs发育的表观遗传规律，并进一步筛选出参与调控hFGCs时空发育的特异性增强子元件，进而通过功能性实验最终明确这些特定调控元件在hFGCs发育分化过程中的具体生物学功能和作用机制。本研究将加深对人类胚胎生殖细胞命运转变及其表观调控机制的理解，对胚胎生殖发育和临床相关疾病的诊疗具有重要指导意义。

The abnormal development of germ cells is closely related to recurrent abortion and termination of pregnancy. Fetal germ cells are important cell types which transmit genetic and epigenetic information between generations and maintain the continuation of a species. Our previous study revealed the transcriptional landscapes of human fetal germ cells (hFGCs). However, we still know little about the mechanism of epigenetic regulation during the specification of each phase of hFGCs. Here we use single cell multi-omics sequencing technique (scCOOL-seq) and thorough bioinformatics analysis to reveal the dynamic pattern of DNA methylation and chromatin accessibility of each phase of hFGCs along development. Most importantly, identifying the phase-specific regulatory elements that control the cell-fate transition of hFGCs and investigating the functional mechanism of each regulatory element. Overall, we anticipate that our study will refresh the understanding of the molecular mechanism of epigenetic regulation during the development and phase transition of hFGCs and greatly impact on ways toward developing new strategies to diagnose and treat the germ-line related diseases.