Spatiotemporally primed coelomic epithelium and supporting-like cells establish the dual origin of granulosa cells
Abstract
Ovarian organogenesis relies on the coordinated specification of supporting and steroidogenic lineages from multipotent progenitors of the coelomic epithelium. However, how these progenitors adopt distinct fates and differentiate into pregranulosa cells and steroidogenic progenitors of theca cells remain poorly understood. Here, we show that the dynamics of ovarian somatic lineage specification are conserved between human and mouse. Coelomic epithelial cells covering the fetal ovaries are heterogeneous and already biased toward supporting or steroidogenic fates. This priming is spatially and temporally organized, influenced by proximity to the mesonephros, and characterized by a transient coexistence of both progenitor types before resolving into predominantly supporting-biased cells. In mice, local delamination of these primed epithelial progenitors seeds intragonadal domains that give rise to pregranulosa and steroidogenic progenitors. We further demonstrate that these fetal steroidogenic progenitors generate adult stromal and theca cells. In addition, we uncover that granulosa cells arise from two distinct sources: Coelomic epithelium–derived progenitors generate the majority of cortical granulosa cells forming the long-lived follicle reserve, whereas supporting-like cells contribute to a smaller granulosa subpopulation. Together, these findings establish a revised model of ovarian development in which early spatial patterning of coelomic epithelial progenitors directs lineage specification, reveals the dual origin of granulosa cells, and defines the developmental origin of theca cells.
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BibTeX
@article{djari2026spatiotemporally,
title = {{Spatiotemporally primed coelomic epithelium and supporting-like cells establish the dual origin of granulosa cells}},
author = {Cyril Djari and Chloé Mayère and Maëva Guy and Aitana Perea-Gómez and Laura Bellutti and Paul Barreau and Herta Ademi and Agathe Rozier and Anthony S Martinez and Tyler J Gibson and Françoise Kühne and Cassandre Guérin and Dagmar Wilhelm and Gabriel Livera and Jennifer Mckey and Marie-Christine Chaboissier and Serge Nef},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = sep,
doi = {10.1073/pnas.2615939123},
url = {https://hal.science/hal-05769020v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spatiotemporally primed coelomic epithelium and supporting-like cells establish the dual origin of granulosa cells
AU - Cyril Djari
AU - Chloé Mayère
AU - Maëva Guy
AU - Aitana Perea-Gómez
AU - Laura Bellutti
AU - Paul Barreau
AU - Herta Ademi
AU - Agathe Rozier
AU - Anthony S Martinez
AU - Tyler J Gibson
AU - Françoise Kühne
AU - Cassandre Guérin
AU - Dagmar Wilhelm
AU - Gabriel Livera
AU - Jennifer Mckey
AU - Marie-Christine Chaboissier
AU - Serge Nef
PY - 2026
DA - 2026/09/28
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2615939123
UR - https://hal.science/hal-05769020v1
AB - Ovarian organogenesis relies on the coordinated specification of supporting and steroidogenic lineages from multipotent progenitors of the coelomic epithelium. However, how these progenitors adopt distinct fates and differentiate into pregranulosa cells and steroidogenic progenitors of theca cells remain poorly understood. Here, we show that the dynamics of ovarian somatic lineage specification are conserved between human and mouse. Coelomic epithelial cells covering the fetal ovaries are heterogeneous and already biased toward supporting or steroidogenic fates. This priming is spatially and temporally organized, influenced by proximity to the mesonephros, and characterized by a transient coexistence of both progenitor types before resolving into predominantly supporting-biased cells. In mice, local delamination of these primed epithelial progenitors seeds intragonadal domains that give rise to pregranulosa and steroidogenic progenitors. We further demonstrate that these fetal steroidogenic progenitors generate adult stromal and theca cells. In addition, we uncover that granulosa cells arise from two distinct sources: Coelomic epithelium–derived progenitors generate the majority of cortical granulosa cells forming the long-lived follicle reserve, whereas supporting-like cells contribute to a smaller granulosa subpopulation. Together, these findings establish a revised model of ovarian development in which early spatial patterning of coelomic epithelial progenitors directs lineage specification, reveals the dual origin of granulosa cells, and defines the developmental origin of theca cells.
SN - 0027-8424
SN - 1091-6490
ER -