{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:28:51Z","timestamp":1787005731309,"version":"build-2736575974"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM119458"],"award-info":[{"award-number":["R35GM119458"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD094698"],"award-info":[{"award-number":["R01HD094698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012756","name":"Lalor Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100012756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:p>\n                    Supporting cells of the ovary, termed granulosa cells, are essential for ovarian differentiation and oogenesis by providing a nurturing environment for oocyte maintenance and maturation. Granulosa cells are specified in the fetal and perinatal ovary, and sufficient numbers of granulosa cells are critical for the establishment of follicles and the oocyte reserve. Identifying the cellular source from which granulosa cells and their progenitors are derived is an integral part of efforts to understand basic ovarian biology and the etiology of female infertility. In particular, the contribution of mesenchymal cells, especially perivascular cells, to ovarian development is poorly understood but is likely to be a source of new information regarding ovarian function. Here we have identified a cell population in the fetal ovary, which is a Nestin-expressing perivascular cell type. Using lineage tracing and ex vivo organ culture methods, we determined that perivascular cells are multipotent progenitors that contribute to granulosa, thecal, and pericyte cell lineages in the ovary. Maintenance of these progenitors is dependent on ovarian vasculature, likely reliant on endothelial\u2013mesenchymal Notch signaling interactions. Depletion of Nestin\n                    <jats:sup>+<\/jats:sup>\n                    progenitors resulted in a disruption of granulosa cell specification and in an increased number of germ cell cysts that fail to break down, leading to polyovular ovarian follicles. These findings highlight a cell population in the ovary and uncover a key role for vasculature in ovarian differentiation, which may lead to insights into the origins of female gonad dysgenesis and infertility.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2213026119","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T13:33:01Z","timestamp":1664890381000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Perivascular cells support folliculogenesis in the developing ovary"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6172-784X","authenticated-orcid":false,"given":"Shu-Yun","family":"Li","sequence":"first","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidur","family":"Bhandary","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Gu","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-7040","authenticated-orcid":false,"given":"Tony","family":"DeFalco","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00009.2006"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2019.02.004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0062"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00174"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.095208"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.08.013"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005570117"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10783"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.07.026"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.05.019"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707674105"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010299108"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.10.040"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06996-3"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052620"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10128"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.078071"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14936-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00677"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.06.003"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0689"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.27708"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4144-6"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.149"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200409107"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(10)90007-0"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.02.069"},{"key":"e_1_3_4_28_2","first-page":"654","article-title":"Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases","volume":"8","author":"Ikeda Y.","year":"1994","unstructured":"Y. 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