Beijing Advanced Innovation Center for Genomics (ICG), College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence and Center for Reproductive Medicine, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
Beijing Advanced Innovation Center for Genomics (ICG), College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
Cell Stem Cell. 2017 Jun 1;20(6):858-873.e4. doi: 10.1016/j.stem.2017.03.007. Epub 2017 Apr 27.
Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here we performed single-cell RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and male human embryos spanning several developmental stages. We found that female FGCs undergo four distinct sequential phases characterized by mitosis, retinoic acid signaling, meiotic prophase, and oogenesis. Male FGCs develop through stages of migration, mitosis, and cell-cycle arrest. Individual embryos of both sexes simultaneously contain several subpopulations, highlighting the asynchronous and heterogeneous nature of FGC development. Moreover, we observed reciprocal signaling interactions between FGCs and their gonadal niche cells, including activation of the bone morphogenic protein (BMP) and Notch signaling pathways. Our work provides key insights into the crucial features of human FGCs during their highly ordered mitotic, meiotic, and gametogenetic processes in vivo.
人类胚胎生殖细胞（FGCs）是精子和卵子的前体细胞，对于物种的维持至关重要。然而，人类 FGCs 的发育轨迹和异质性在很大程度上仍然未知。在这里，我们对跨越多个发育阶段的女性和男性人类胚胎中的 2000 多个 FGC 及其性腺巢细胞进行了单细胞 RNA-seq 分析。我们发现，女性 FGC 经历了四个不同的连续阶段，其特征是有丝分裂、视黄酸信号、减数分裂前期和卵子发生。男性 FGC 通过迁移、有丝分裂和细胞周期阻滞阶段发育。两性个体的胚胎同时包含多个亚群，突出了 FGC 发育的异步和异质性。此外，我们观察到 FGC 与其性腺巢细胞之间的相互信号传递相互作用，包括骨形态发生蛋白（BMP）和 Notch 信号通路的激活。我们的工作为人类 FGC 在体内高度有序的有丝分裂、减数分裂和配子发生过程中的关键特征提供了重要的见解。
