Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions

• DOI: 10.1016/j.stem.2017.03.007
• Publication Date: 2017-04-27T16:00:22Z
• Authors: Li Li; Ji Dong; Liying Yan; Jun Yong; Xixi Liu; Yuqiong Hu; Xiaoying Fan; Xinglong Wu; Hongshan Guo; Xiaoye Wang; Xiaohui Zhu; Rong Li; Jie Yan; Yuan Wei; Yangyu Zhao; Wei Wang; Yixin Ren; Peng Yuan; Zhiqiang Yan; Boqiang Hu; Fan Guo; Lu Wen; Fuchou Tang; Jie Qiao
• Keywords: Male; 0303 health sciences; Receptors, Notch; High-Throughput Nucleotide Sequencing; Embryonic Germ Cells; 03 medical and health sciences; Fetus; Bone Morphogenetic Proteins; Humans; Female; Stem Cell Niche; Gonads; Cell Division; Signal Transduction

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.