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

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
Cell research | 2021

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.

Pubmed ID: 32884136

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


SAMTOOLS (tool)

RRID:SCR_002105

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RRID:SCR_005604

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RRID:SCR_008984

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PBAT (tool)

RRID:SCR_009105

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HOMER (tool)

RRID:SCR_010881

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