biostudies-literatureGuahmich NLNCATS NIH HHSU.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development7https://www.ebi.ac.uk/biostudies/studies/S-EPMC9812973biostudies-literatureUnknown6(1)Theca cells serve multiple essential functions during the growth and maturation of ovarian follicles, providing structural, metabolic, and steroidogenic support. While the function of theca during folliculogenesis is well established, their cellular origins and the differentiation hierarchy that generates distinct theca sub-types, remain unknown. Here, we performed single cell multi-omics analysis of primary cell populations purified from human antral stage follicles (1-3 mm) to define the differentiation trajectory of theca/stroma cells. We then corroborated the temporal emergence and growth kinetics of defined theca/stroma subpopulations using human ovarian tissue samples and xenografts of cryopreserved/thawed ovarian cortex, respectively. We identified three lineage specific derivativesCommunications biologyHuman theca arises from ovarian stroma and is comprised of three discrete subtypes.PMC9812973UL1 TR002384R21 HD103956-01A1Zhang KKallinos EArazi LSchattman GJames DMan LTopper-Kroog AWang JStewart JGuahmich NLSchatz-Siemers NBodine RGrullon GJones SHZaninovic NRosenwaks ZfalseHuman theca arises from ovarian stroma and is comprised of three discrete subtypes.Theca cells serve multiple essential functions during the growth and maturation of ovarian follicles, providing structural, metabolic, and steroidogenic support. While the function of theca during folliculogenesis is well established, their cellular origins and the differentiation hierarchy that generates distinct theca sub-types, remain unknown. Here, we performed single cell multi-omics analysis of primary cell populations purified from human antral stage follicles (1-3 mm) to define the differentiation trajectory of theca/stroma cells. We then corroborated the temporal emergence and growth kinetics of defined theca/stroma subpopulations using human ovarian tissue samples and xenografts of cryopreserved/thawed ovarian cortex, respectively. We identified three lineage specific derivatives2023-01-01T00:00:00Z2023 Jan2026-05-28T03:45:35.671Z2025-04-06T00:53:09.302ZS-EPMC98129733659997010.1038/s42003-022-04384-8