Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions.
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
Author Information
Li Li: 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.
Ji Dong: 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.
Liying Yan: 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.
Jun Yong: 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.
Xixi Liu: 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.
Yuqiong Hu: 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; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Xiaoying Fan: 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.
Xinglong Wu: 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.
Hongshan Guo: 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.
Xiaoye Wang: 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.
Xiaohui Zhu: 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.
Rong Li: 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.
Jie Yan: 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.
Yuan Wei: 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.
Yangyu Zhao: 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.
Wei Wang: 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.
Yixin Ren: 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.
Peng Yuan: 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.
Zhiqiang Yan: 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.
Boqiang Hu: 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.
Fan Guo: 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.
Lu Wen: 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.
Fuchou Tang: 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; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: tangfuchou@pku.edu.cn.
Jie Qiao: 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; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: jie.qiao@263.net.
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.
