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

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.

Keywords: Leydig cell; Sertoli cell; germ cell; germline; gonad; granulosa cell; oocyte; ovary; single-cell RNA sequencing; testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Proteins / metabolism
  • Cell Division / physiology*
  • Embryonic Germ Cells / cytology
  • Embryonic Germ Cells / metabolism*
  • Female
  • Fetus / cytology
  • Fetus / metabolism*
  • Gonads / cytology
  • Gonads / enzymology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology*
  • Stem Cell Niche / physiology*


  • Bone Morphogenetic Proteins
  • Receptors, Notch