This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A new study has mapped human urogenital development in its native spatial context, revealing how neighboring organs coordinate their development through cellular communication and molecular signaling during embryogenesis. The study, published in Science, was led by Guo Jingtao and Wang Xiaoyan at the Institute of Zoology of the Chinese Academy of Sciences, in collaboration with researchers from Peking University Third Hospital and the Women and Children's Hospital, Qingdao University.
The urinary and reproductive systems share embryonic origins and develop in close physical proximity. During the fourth to fifth weeks, the intermediate mesoderm forms the mesonephros, adrenal primordium and gonadal primordium. Single-cell studies have clarified cell types and developmental trajectories within individual organs.
However, tissue dissociation removes the spatial relationships needed to study communication across organ boundaries. To investigate the coordinated development of the human urogenital system within its native spatial context, the researchers combined high-resolution spatial transcriptomics with single-cell multi-omics, tissue protein imaging and human embryonic stem cell models to analyze male and female human embryos at Carnegie stages 15, 19 and 23. These stages span gonadal specification and sex differentiation.
Stereo-seq profiling and spatially informed clustering resolved major gonadal, adrenal cortical, renal, mesenchymal and neural populations. The analysis further classified the dataset into 33 cell types. Developmental trajectories suggest that renal lineages diverge relatively early, while adrenal cortical and gonadal somatic lineages remain more closely related.
At Carnegie stage 15 (CS15), spatial cell-communication analysis showed that the gonadal primordium receives WNT, BMP and NCAM signals from nearby tissues including the mesonephros and adrenal primordium. Guided by the spatial data, the team treated human embryonic stem cell–derived intermediate mesoderm with BMP7, NCAM1 and CHIR99021. The three-factor combination increased early gonadal marker expression and shifted the transcriptome toward an in vivo early gonadal state.
These results suggest that neighboring tissues can help shape early gonadal fate. As development progresses, the gonads remain spatially adjacent to the mesonephros. In the region where the rete testis or rete ovarii forms, the team identified PAX8-expressing rete cells.
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