Integrated analysis and systematic characterization of the regulatory network for human germline development

作者：Yashi Gu, Jiayao Chen, Ziqi Wang, Qizhe Shao, Zhekai Li, Yaxuan Ye, Xia Xiao, Yitian Xiao, Wenyang Liu, Sisi Xie, Lingling Tong, Jin Jiang, Xiaoying Xiao, Ya Yu, Min Jin, Yanxing Wei, Robert S. Young, Lei Hou, Di Chen · 发表于：Journal of genetics and genomics/Journal of Genetics and Genomics · 年份：2024 · DOI：10.1016/j.jgg.2024.11.005 · 被引用次数：7 · 研究领域：Animal Genetics and Reproduction、Pluripotent Stem Cells Research、CRISPR and Genetic Engineering

Primordial germ cells (PGCs) are the precursors of germline that are specified at the embryonic stage. Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice. Moreover, the specific regulatory machinery remains largely unexplored, mainly due to the inaccessible nature of this complex biological process in humans. Here, we curate and integrate multi-omics data, including 581 RNA-seq, 54 ATAC-seq, 45 ChIP-seq, and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process, presenting an atlas in the human PGC database (hPGCdb). With these uniformly processed data and integrated analyses, we characterize the potential key transcription factors and regulatory networks governing human germ cell fate. We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown. We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development, as well as soma-derived NOTCH2 signaling for germ cell differentiation. Taken together, we have built a database for human PGCs (http://43.131.248.15:6882) and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development, including both intrinsic and extrinsic regulatory programs.