Single-cell transcriptomic profiling redefines the origin and specification of early adrenogonadal progenitors

Adrenal cortex and gonads represent the two major steroidogenic organs in mammals. Both tissues are considered to share a common developmental origin characterized by the expression of Nr5a1/Sf1. The pre-cise origin of adrenogonadal progenitors and the processes driving differentiation toward the adrenal or gonadal fate remain, however, elusive. Here, we provide a comprehensive single-cell transcriptomic atlas of early mouse adrenogonadal development including 52 cell types belonging to twelve major cell lineages. Trajectory reconstruction reveals that adrenogonadal cells emerge from the lateral plate rather than the in-termediate mesoderm. Surprisingly, we find that gonadal and adrenal fates have already diverged prior to Nr5a1 expression. Finally, lineage separation into gonadal and adrenal fates involves canonical versus non-canonical Wnt signaling and differential expression of Hox patterning genes. Thus, our study provides important insights into the molecular programs of adrenal and gonadal fate choice and will be a valuable resource for further research into adrenogonadal ontogenesis.

Automated summary

This study provides a comprehensive single-cell transcriptomic atlas of early mouse adrenogonadal development, revealing the differentiation process and molecular mechanisms. It is found that the fate of adrenal and gonadal has diverged prior to Nr5a1 expression and involves differential expression of genes related to Wnt signaling and Hox patterning. This study provides important insights into the ontogenesis of adrenal and gonadal and will be a valuable resource for further research.