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. Electronic address: ksasaki@upenn.edu.
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. Electronic address: saitou@anat2.med.kyoto-u.ac.jp.
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.
