Supporting-like cells constitute an alternative steroidogenic lineage conserved in amniotes
Year: 2026
Type: preprint
Abstract: ABSTRACT In mammals, the production of sex hormones is widely considered to depend on the interstitial lineage of the gonad, which differentiates into Leydig cells in males or theca cells in females. However, certain mammalian species evidence gonadal steroidogenic activity prior to the specialization of these interstitial lineages, suggesting that alternative cell types may assume this function. Here we reveal a previously unrecognized role for supporting-like cells (SLCs), which can act as a major steroidogenic lineage during mammalian embryonic development. Through comparative single-cell transcriptomics, steroidomics and in toto organ imaging we find that in rabbits, SLCs not only contribute to the formation of gonadal rete structures, as described for other mammals, but also differentiate into a steroid-producing population. The steroidogenic program of SLCs is initially activated in both sexes but selectively maintained in ovaries, whereas in testes it is progressively replaced by that of interstitially derived Leydig cells. Evolutionary comparisons indicate that SLCs may represent an ancestral lineage that is homologous to the steroidogenic cells of non-mammalian species, which also derive from supporting precursors and share expression of cell fate regulators such as PAX2/8 and TBX1. Altogether, our findings redefine current models of gonadal lineages, revealing an unexpected plasticity in sex differentiation and exemplifying how distinct cell types can converge on analogous functions during evolution.
Institutions: Consejo Superior de Investigaciones Científicas, Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Max Delbrück Center, Institute of Molecular and Clinical Ophthalmology Basel, École Nationale Vétérinaire d'Alfort, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, University of Kansas Medical Center, Biologie de la Reproduction, Environnement, Epigénétique et Développement, University of Geneva, Swiss Centre for Applied Human Toxicology, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Intégrative de la Cellule, University of Colorado Anschutz
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: RNA Helicase function in vertebrate sex-determination and human Disorders of Sex Development (DSD), Retinoic acid for germ cell differentiation and meiosis, The PAX8/SOX9/WNT4 triad as master regulators of Supporting-Like Cells (SLC) specification and rete testis formation in mammals, Investigating gonadal sex differentiation by single cell transcriptomics in mice and humans, Revisiting adreno-gonadal development and cell fate commitment using single cell RNA sequencing, Functions of the rete ovarii in ovary development, adult homeostasis, and female reproductive longevity
OpenAlex ID: W7162690698