Generation of human oogonia from induced pluripotent stem cells in vitro

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellular Reprogramming Techniques / methods*
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Oogenesis*
  • Oogonia / cytology*
  • Ovary / growth & development*