Initiation of meiosis from human iPSCs under defined conditions through identification of regulatory factors.

ABSTRACT: Meiotic failure is a major cause of infertility, but the lack of an in vitro model of human meiosis is a barrier to understanding its mechanism. Here, we establish a method to initiate meiosis directly from male or female human-induced pluripotent stem cells (iPSCs). DNMT1 inhibition, retinoid signaling activation, and overexpression of regulatory factors (antiapoptotic BCL2 and promeiotic HOXB5, BOLL, or MEIOC) rapidly activates meiosis over a 15-day protocol. 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

SUBMITTER: Smela MP 

PROVIDER: S-EPMC12356269 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature