{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:12:48Z","timestamp":1788264768867,"version":"build-2803163510"},"reference-count":104,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100022932","name":"National Stem Cell Foundation of Australia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022932","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020071","name":"Cybec Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100020071","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Reproductive development is a complex process orchestrated by precise gene expression and cellular interactions. Disruption to this process can result in differences of sex development (DSDs) which occur in approximately 1-2% of live births. We have previously developed a protocol to differentiate human induced pluripotent stem cells (hiPSCs) into testis-like organoids. In this study, we performed bulk and single-cell RNA-sequencing on these organoids to investigate their transcriptional landscape. Transcriptomic analysis revealed six distinct cell clusters expressing markers associated with bipotential, early Sertoli and testicular interstitial cells. These findings provide the first comprehensive transcriptional profile of hiPSC-derived testis-like organoids. Additionally, to address the limited emergence of mature cell types, we generated an inducible NR5A1\/SF1 hiPSC line, which successfully triggered the upregulation of Leydig cell markers and additional Sertoli markers upon overexpression. Our findings show that our testis-like organoids are a valuable model system for studying DSDs in vitro.<\/jats:p>","DOI":"10.1242\/dev.204772","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:11:21Z","timestamp":1771834281000},"source":"Crossref","is-referenced-by-count":2,"title":["The emergence of multiple testicular cell lineages in human stem cell-derived testis-like organoids"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9116-6064","authenticated-orcid":false,"given":"Svenja","family":"Pachernegg","sequence":"first","affiliation":[{"name":"Murdoch Children's Research Institute 1 Reproductive Development , , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"University of Melbourne 2 Department of Paediatrics , , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Murdoch Children's Research Institute 3 Transcriptomics and Bioinformatics , , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"Novo Nordisk Foundation Centre for Stem Cell Medicine, Murdoch Children's Research Institute 4 , Parkville, VIC 3052 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorjana","family":"Robevska","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute 1 Reproductive Development , , Parkville, VIC 3052 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas G. 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Children's Research Institute 3 Transcriptomics and Bioinformatics , , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"Novo Nordisk Foundation Centre for Stem Cell Medicine, Murdoch Children's Research Institute 4 , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"University of Melbourne 8 Department of Clinical Pathology , , Parkville, VIC 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Rollo","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University 5 Department of Neuroscience , , Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa H.","family":"Little","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Centre for Stem Cell Medicine, Murdoch Children's Research Institute 4 , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"Novo Nordisk Foundation Centre for Stem Cell Medicine 7 , Faculty of Health and Medical Sciences , , 2200 Copenhagen ,","place":["Denmark"]},{"name":"University of Copenhagen 7 , Faculty of Health and Medical Sciences , , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirana","family":"Ramialison","sequence":"additional","affiliation":[{"name":"University of Melbourne 2 Department of Paediatrics , , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Murdoch Children's Research Institute 3 Transcriptomics and Bioinformatics , , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"Novo Nordisk Foundation Centre for Stem Cell Medicine, Murdoch Children's Research Institute 4 , Parkville, VIC 3052 ,","place":["Australia"]},{"name":"Australian Regenerative Medicine Institute, Monash University 9 , Clayton, VIC 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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