Generation of human oogonia from induced pluripotent stem cells in vitro

Chika Yamashiro, Kotaro Sasaki, Yukihiro Yabuta, Yoji Kojima, Tomonori Nakamura, Ikuhiro Okamoto, Shihori Yokobayashi, Yusuke Murase, Yukiko Ishikura, Kenjiro Shirane, Hiroyuki Sasaki, Takuya Yamamoto, Mitinori Saitou

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)356-360
Number of pages5
JournalScience
Volume362
Issue number6412
DOIs
Publication statusPublished - Oct 19 2018

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Generation of human oogonia from induced pluripotent stem cells in vitro'. Together they form a unique fingerprint.

  • Cite this

    Yamashiro, C., Sasaki, K., Yabuta, Y., Kojima, Y., Nakamura, T., Okamoto, I., Yokobayashi, S., Murase, Y., Ishikura, Y., Shirane, K., Sasaki, H., Yamamoto, T., & Saitou, M. (2018). Generation of human oogonia from induced pluripotent stem cells in vitro. Science, 362(6412), 356-360. https://doi.org/10.1126/science.aat1674