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.
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.
Cell Rep. 2021 May 4;35(5):109075. doi: 10.1016/j.celrep.2021.109075.
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.
在胚胎早期，性腺具有双能性，只有在遗传性别决定后才会成为卵巢或睾丸。尽管有许多研究探讨了双能性腺是如何决定性别，但双能性腺及其祖细胞的空间和时间组织仍知之甚少。在这里，我们通过在小鼠中进行谱系追踪，发现性腺起源于 T 原始条纹，通过 WT1 后中胚层，并在前部与肾上腺和后部与后肾间充质共享起源。在小鼠和食蟹猴胚胎中的比较单细胞转录组分析揭示了伴随双能性腺祖细胞特化的谱系轨迹和遗传程序的趋同。这个过程涉及上皮基因的持续表达和间充质基因的上调，从而赋予了上皮-间充质混合状态。我们的研究为理解小鼠和灵长类动物早期性腺发生提供了关键资源。
