Spatial coordination in the codevelopment of the human urogenital system during organogenesis

The human urogenital system originates from a common embryonic domain, yet the mechanisms guiding its spatiotemporal coordination remain understudied. Here, we combined high-resolution spatial transcriptomics with single-cell multiomics to profile human embryos from Carnegie stages 15 to 23, capturing the codevelopmental dynamics of the urogenital system. We revealed mesonephros- and adrenal primordium–derived signals that promote gonadal specification and enable efficient in vitro generation of cells resembling early gonadal lineages. We also uncovered a possible mesonephric origin of gonadal supporting cells through rete testis or ovarii linking the mesonephros. Finally, we delineate three transcriptionally distinct steroidogenic lineages differing in cholesterol sourcing, cortisol synthesis, and sex hormone production that together orchestrate sex differentiation. These findings deepen our understanding of urogenital system assembly and guide the exploration of coordinated multiorgan development.