Dissecting the epigenomic dynamics of human fetal germ cell development at single-cell resolution  

作　　者：Li Li Lin Li Qingqing Li Xixi Liu Xinyi Ma Jun Yong Shuai Gao Xinglong Wu Yuan Wei Xiaoye Wang Wei Wang Rong Li Jie Yan Xiaohui Zhu Lu Wen Jie Qiao Liying Yan Fuchou Tang 

机构地区：[1]Beijing Advanced Innovation Center for Genomics,Department of Obstetrics and Gynecology,Third Hospital,School of Life Sciences,Peking University,Beijing,100871,China [2]Biomedical Pioneering Innovation Center,Center for Reproductive Medicine,Ministry of Education,Key Laboratory of Cell Proliferation and Differentiation,Beijing,100871,China [3]Department of Pathophysiology,Guangdong Provincial Key Laboratory of Proteomics,School of Basic Medical Sciences,Southern Medical University,Guangzhou,Guangdong,510515,China [4]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology,Beijing,100191,China [5]Key Laboratory of Assisted Reproduction,Ministry of Education,Beijing,100191,China [6]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing,100871,China [7]Stem Cell Program,Boston Children's Hospital,Boston,MA 02115,USA [8]Department of Stem Cell and Regenerative Biology,Harvard University,Cambridge,MA 02138,USA

出　　处：《Cell Research》2021年第4期463-477,共15页细胞研究（英文版）

基　　金：The study was supported by the Beijing Advanced Innovation Center for Genomics at Peking University;We sincerely thank Fei Wang and Xuefang Zhang from the National Center for Protein Sciences Beijing(Peking University)for assisting with the FACS analysis;Part of the bioinformatic analyses were run on the Computing Platform of the Center for Life Science;The study was supported by the Beijing Municipal Science and Technology Commission(Z181100001318001);the National Natural Science Foundation of China(31625018,31890781,81521002 and 81730038);the National Basic Research Program of China(2018YFA0107601,2018YFC1004000 and 2017YFA0102702).

摘　　要：Proper development of fetal germ cells(FGCs)is vital for the precise transmission of genetic and epigenetic information through generations.The transcriptional landscapes of human FGC development have been revealed;however,the epigenetic reprogramming process of FGCs remains elusive.Here,we profiled the genome-wide DNA methylation and chromatin accessibility of human FGCs at different phases as well as gonadal niche cells at single-cell resolution.First,we found that DNA methylation levels of FGCs changed in a temporal manner,whereas FGCs at different phases in the same embryo exhibited comparable DNA methylation levels and patterns.Second,we revealed the phase-specific chromatin accessibility signatures at the promoter regions of a large set of critical transcription factors and signaling pathway genes.We also identified potential distal regulatory elements including enhancers in FGCs.Third,compared with other hominid-specific retrotransposons,SVA_D might have a broad spectrum of binding capacity for transcription factors,including SOX15 and SOX17.Finally,using an in vitro culture system of human FGCs,we showed that the BMP signaling pathway promoted the cell proliferation of FGCs,and regulated the WNT signaling pathway by orchestrating the chromatin accessibility of its ligand genes.Our single-cell epigenomic atlas and functional assays provide valuable insights for understanding the strongly heterogeneous,unsynchronized,yet highly robust nature of human germ cell development.

关 键 词：FETAL PRECISE LANDSCAPE 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]