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Direct induction of meiosis from human iPSCs under defined conditions

GSE286688 Homo sapiens Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2025/01/15 Platform GPL34284
Summary
Meiotic failure is a significant 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 (anti-apoptotic BCL2, and pro-meiotic 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 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.
Published in
Initiation of meiosis from human iPSCs under defined conditions through identification of regulatory factors
Smela MP, Adams J, Ma C et al. · Science advances 2025 · PMID 40815662 · doi:10.1126/sciadv.adu0384
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Also filed as BioProject PRJNA1209977 and SRA study SRP557068. Searching any of these in the dataset finder brings you back here.

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