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Our protocol bypasses the primordial germ cell stage and directly generates cells expressing genes similar to meiotic oogonia, including oogonia markers, all synaptonemal complex components, and meiotic recombination machinery. DNMT1 inhibition rapidly erases DNA methylation, including at imprinting control regions and promoters of meiotic genes. Microscopy shows key aspects of meiosis, including chromosome axis formation and synapsis in live human cells. Our model of human meiosis provides opportunities for studying this critical reproductive process under chemically defined conditions in vitro.<\/jats:p>","DOI":"10.1126\/sciadv.adu0384","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T17:58:28Z","timestamp":1755280708000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Initiation of meiosis from human iPSCs under defined conditions through identification of regulatory factors"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-7098","authenticated-orcid":true,"given":"Merrick Pierson","family":"Smela","sequence":"first","affiliation":[{"name":"Wyss Institute, Harvard University, Boston, MA 02215, USA."},{"name":"Ovelle Bio, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Adams","sequence":"additional","affiliation":[{"name":"Wyss Institute, Harvard University, Boston, MA 02215, USA."},{"name":"Ovelle Bio, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1016-9278","authenticated-orcid":true,"given":"Carl","family":"Ma","sequence":"additional","affiliation":[{"name":"Wyss Institute, Harvard University, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-5749","authenticated-orcid":true,"given":"Laura","family":"Breimann","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0886-9045","authenticated-orcid":true,"given":"Ursula","family":"Widocki","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7052-4091","authenticated-orcid":true,"given":"Bogdan","family":"Dobre","sequence":"additional","affiliation":[{"name":"Ovelle Bio, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Shioda","sequence":"additional","affiliation":[{"name":"Krantz Family Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-9969","authenticated-orcid":true,"given":"George M.","family":"Church","sequence":"additional","affiliation":[{"name":"Wyss Institute, Harvard University, Boston, MA 02215, USA."},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.88"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.07.019"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","unstructured":"H. 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