Cell Reports 2023 Feb 28;42(3):112191. DOI: 10.1016/j.celrep.2023.112191

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

Yasmine Neirijnck¹, Pauline Sararols², Françoise Kühne², Chloé Mayère², Lahiru Chamara Weerasinghe Arachchige³, Violaine Regard², Serge Nef⁴, Andreas Schedl⁵

 

Affiliations

¹Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Université Côte d’Azur, CNRS, INSERM, IBV, 06108 Nice, France
²Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland
³Université Côte d’Azur, CNRS, INSERM, IBV, 06108 Nice, France
⁴Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland
⁵Université Côte d’Azur, CNRS, INSERM, IBV, 06108 Nice, France

 

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, 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.

DOI: 10.1038/s41467-023-36644-4