Supporting-like cells constitute an alternative steroidogenic lineage conserved in amniotes
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.
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BibTeX
@misc{barberaaura2026supportinglike,
title = {{Supporting-like cells constitute an alternative steroidogenic lineage conserved in amniotes}},
author = {Iván Barberá-Aura and Wai-Yee Chung and Emilie Dujardin and Alicia Hurtado and Mathieu Galmiche and Chloé Mayère and Maëva Guy and Béatrice Mandon-Pépin and Vedran Franke and Yan Jaszczyszyn and Rafael D. Acemel and Serge Rudaz and Jennifer Mckey and Serge Nef and Eric Pailhoux and Darío G. Lupiáñez},
howpublished = {bioRxiv (Cold Spring Harbor Laboratory)},
year = {2026},
month = nov,
doi = {10.64898/2026.05.25.726204},
url = {https://hal.science/hal-05850371v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Supporting-like cells constitute an alternative steroidogenic lineage conserved in amniotes
AU - Iván Barberá-Aura
AU - Wai-Yee Chung
AU - Emilie Dujardin
AU - Alicia Hurtado
AU - Mathieu Galmiche
AU - Chloé Mayère
AU - Maëva Guy
AU - Béatrice Mandon-Pépin
AU - Vedran Franke
AU - Yan Jaszczyszyn
AU - Rafael D. Acemel
AU - Serge Rudaz
AU - Jennifer Mckey
AU - Serge Nef
AU - Eric Pailhoux
AU - Darío G. Lupiáñez
PY - 2026
DA - 2026/11/03
PB - bioRxiv (Cold Spring Harbor Laboratory)
DO - 10.64898/2026.05.25.726204
UR - https://hal.science/hal-05850371v1
AB - 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.
ER -