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

Abstract

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 precise 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 intermediate mesoderm. Surprisingly, gonadal and adrenal fates show distinct molecular signatures upon Nr5a1 induction indicating the two tissues are specified independently. Finally, lineage separation into gonadal and adrenal fate 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 early adrenogonadal ontogenesis.