{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:41:16Z","timestamp":1788374476555,"version":"build-2803163510"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD090660"],"award-info":[{"award-number":["R01 HD090660"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"10.13039\/100000054","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":[[2025,6,10]]},"abstract":"<jats:p>\n                    Historically, endocrine cells were perceived to coordinate their output in a uniform manner. Recently however, single-cell technologies have uncovered heterogeneity within these populations, indicating that individual cells may operate as independently regulated units. Using high-resolution tools such as single-molecule fluorescent in situ hybridization (sm-FISH) and single-cell RNA sequencing (scRNA-seq), we investigated the contributions of individual and the collective of fetal Leydig cells to androgen production over time during mouse testis development. Temporal profiles of intratesticular androgens alongside the expression of steroidogenic pathway genes (\n                    <jats:italic toggle=\"yes\">Star, Cyp11a1, Cyp17a1,<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Hsd3b1<\/jats:italic>\n                    ) from prenatal to perinatal testes demonstrated that the peak in gene expression preceded the peak in androgen production. Spatially, steroidogenic cells were initially observed to be concentrated toward the anterior\u2013posterior poles along the center of the dorsal\u2013ventral axis of the fetal testis at embryonic day (E) 13 and then expanded to a uniform distribution by E16. Next, sm-FISH using probes for individual steroidogenic pathway genes exposed the following findings: gene transcription and processing of individual and combinations of steroidogenic pathway genes are not synchronized among fetal Leydig cells; and some fetal Leydig cells express incomplete sets of genes. Further, sm-FISH and scRNA-seq data corroborated the presence of fetal Leydig and other interstitial cell types harboring incomplete sets of steroidogenic pathway genes throughout developmental stages. Taken together, these findings highlight that fetal steroidogenic gene expression is tightly regulated and that transcript presence among interstitial cell types promotes the possibility that optimal androgen biosynthesis results from a cooperative effort among neighboring steroidogenic cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2501392122","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T13:38:28Z","timestamp":1748957908000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Single-cell resolution uncovers neighboring cell subtypes that share steroidogenic capacity during fetal testis development"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-3796","authenticated-orcid":false,"given":"Keer","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin","place":["Madison"]},{"name":"Cellular and Molecular Biology Graduate Program, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-7040","authenticated-orcid":false,"given":"Philippos","family":"Tsourkas","sequence":"additional","affiliation":[{"name":"Cancer Informatics Shared Resource, Carbone Cancer Center, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anbarasi","family":"Kothandapani","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Kearse","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J.","family":"McIlwain","sequence":"additional","affiliation":[{"name":"Cancer Informatics Shared Resource, Carbone Cancer Center, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4886","authenticated-orcid":false,"given":"Chlo\u00e9","family":"May\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Institute of Genetics and Genomics of Geneva, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5462-0676","authenticated-orcid":false,"given":"Serge","family":"Nef","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Institute of Genetics and Genomics of Geneva, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5787-8856","authenticated-orcid":false,"given":"Joan S.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012369415-7\/50013-2"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09400913"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/19382014.2022.2030649"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90211-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(04)33005-6"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00164"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1081\/CBI-120038607"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2015.11.002"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.95103"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm0972"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2008.09.006"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac173"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10508-014-0385-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2040094.047"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-23-0036"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34241"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02602-y"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa215"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.11.003"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12287"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110935"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06996-3"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5238"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.01.011"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23739"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.981202"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1052503"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.169136"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.004"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.7.7545"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012-1256"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.118570"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.04.001"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.16.1.0759"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2406"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.559674"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008810"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.088997"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.825904"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.695546"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.3.5788"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa058"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.12.004"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.058"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.51.32656"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3320293"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.1.0582"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415725"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.2.5754"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047359"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0277"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.4.5861"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.07.030"},{"key":"e_1_3_4_54_2","first-page":"407","article-title":"The role of the mesonephros in cell differentiation and morphogenesis of the mouse fetal testis","volume":"37","author":"Merchant-Larios H.","year":"1993","unstructured":"H. Merchant-Larios, N. Moreno-Mendoza, M. Buehr, The role of the mesonephros in cell differentiation and morphogenesis of the mouse fetal testis. Int. J. Dev. Biol. 37, 407\u2013415 (1993).","journal-title":"Int. J. Dev. Biol."},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117.1.273"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.9068"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1731"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01826"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.08.039"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707674105"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.12.006"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0296"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.01.022"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.08.015"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111265"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-200044033"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037064"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315821"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3878-13.2013"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2501392122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T13:39:24Z","timestamp":1748957964000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2501392122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":69,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2025,6,10]]}},"alternative-id":["10.1073\/pnas.2501392122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2501392122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]},"assertion":[{"value":"2025-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2501392122"}}