The embryonic ontogeny of the gonadal somatic cells in mice and monkeys
Kotaro Sasaki,
Akiko Oguchi,
Keren Cheng,
Yasuhiro Murakawa,
Ikuhiro Okamoto,
Hiroshi Ohta,
Yukihiro Yabuta,
Chizuru Iwatani,
Hideaki Tsuchiya,
Takuya Yamamoto,
Yasunari Seita,
Mitinori Saitou
Affiliations
Kotaro Sasaki
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Akiko Oguchi
RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan
Keren Cheng
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Yasuhiro Murakawa
RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan
Ikuhiro Okamoto
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Hiroshi Ohta
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Yukihiro Yabuta
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Chizuru Iwatani
Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Hideaki Tsuchiya
Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Takuya Yamamoto
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; AMED-CREST, AMED, Tokyo 100-0004, Japan; Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto 606-8507, Japan
Yasunari Seita
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Bell Research Center for Reproductive Health and Cancer, Nagoya 460-0003, Japan
Mitinori Saitou
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Corresponding author
Summary: In the early fetal stage, the gonads are bipotent and only later become the ovary or testis, depending on the genetic sex. Despite many studies examining how sex determination occurs from biopotential gonads, the spatial and temporal organization of bipotential gonads and their progenitors is poorly understood. Here, using lineage tracing in mice, we find that the gonads originate from a T+ primitive streak through WT1+ posterior intermediate mesoderm and appear to share origins anteriorly with the adrenal glands and posteriorly with the metanephric mesenchyme. Comparative single-cell transcriptomic analyses in mouse and cynomolgus monkey embryos reveal the convergence of the lineage trajectory and genetic programs accompanying the specification of biopotential gonadal progenitor cells. This process involves sustained expression of epithelial genes and upregulation of mesenchymal genes, thereby conferring an epithelial-mesenchymal hybrid state. Our study provides key resources for understanding early gonadogenesis in mice and primates.