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Science. 2018 Oct 19;362(6412):356-360. doi: 10.1126/science.aat1674. Epub 2018 Sep 20.

Generation of human oogonia from induced pluripotent stem cells in vitro.

Author information

1
Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
2
Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
3
Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.
4
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
5
Division of Epigenomics, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
6
Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
7
Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), AMED, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
8
Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. saitou@anat2.med.kyoto-u.ac.jp.

Abstract

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.

PMID:
30237246
DOI:
10.1126/science.aat1674
[Indexed for MEDLINE]

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