期刊
SCIENCE
卷 362, 期 6412, 页码 356-359出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aat1674
关键词
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资金
- Japan Society for the Promotion of Science (JSPS) [17H06098]
- JST-ERATO grant [JPMJER1104]
- HEALIOS
- Pythias Fund
- JSPS [25112010, 18H05214]
- Grants-in-Aid for Scientific Research [18H05214, 25112010] Funding Source: KAKEN
Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.
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