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Here, we describe protocols for differentiation of mouse and human pluripotent cells toward gonadal progenitors. Transcriptomic analysis reveals that the in vitro\u2013derived murine gonadal cells are equivalent to embryonic day 11.5 in vivo progenitors. Using similar conditions, Sertoli-like cells derived from 46,XY human induced pluripotent stem cells (hiPSCs) exhibit sustained expression of testis-specific genes, secrete anti-M\u00fcllerian hormone, migrate, and form tubular structures. Cells derived from 46,XY DSD female hiPSCs, carrying an\n                    <jats:italic>NR5A1<\/jats:italic>\n                    variant, show aberrant gene expression and absence of tubule formation. CRISPR-Cas9\u2013mediated variant correction rescued the phenotype. This is a robust tool to understand mechanisms of sex determination and model DSDs.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abn9793","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:58:30Z","timestamp":1672840710000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":45,"title":["In vitro cellular reprogramming to model gonad development and its disorders"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-8324","authenticated-orcid":true,"given":"Nitzan","family":"Gonen","sequence":"first","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel."},{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, 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