浙江大学陈迪等合作报道了人类生殖系发育调控网络的综合分析和系统表征。2024年11月19日出版的《遗传学报》杂志发表了这项成果。

研究人员表示，原始生殖细胞（PGCs）是胚胎期特定的生殖系前体。最近的研究表明，与小鼠等模式生物相比，人类采用不同的PGC规范机制。此外，具体的调控机制在很大程度上仍未被探索，主要是由于这种复杂的生物过程在人类中难以接近的性质。

研究组整理和整合多组学数据，包括581个RNA-seq， 54个ATAC-seq， 45个ChIP-seq和69个单细胞RNA-seq样本，来自人类PGC发展的不同阶段，以概括精确控制和逐步的过程，在人类PGC数据库（hPGCdb）中呈现图谱。通过这些统一处理的数据和综合分析，研究人员描述了控制人类生殖细胞命运的潜在关键转录因子和调控网络。

课题组通过敲低CRISPR，i验证了一些关键因素在生殖细胞发育中的重要作用。研究人员还发现了体细胞-生殖系相互作用网络，并发现SDC2和LAMA4参与PGC的发育，以及体细胞衍生的NOTCH2信号传导参与生殖细胞分化。

总之，该研究组已经建立了一个人类PGCs数据库（http://43.131.248.15:6882），并证明hPGCdb能够识别控制种系发育机制的缺失部分，包括内在和外在的调节程序。

附：英文原文

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

Author: Yanxing Wei d e f, Robert S. Young g h, Lei Hou i, Di Chen a b j

Issue&Volume: 2024/11/19

Abstract: Primordial germ cells (PGCs) are the precursors of germline that are specified at 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.

DOI: 10.1016/j.jgg.2024.11.005

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724003060