論文

査読有り 国際誌
2020年11月2日

Long-term expansion with germline potential of human primordial germ cell-like cells in vitro.

The EMBO journal
  • Yusuke Murase
  • ,
  • Yukihiro Yabuta
  • ,
  • Hiroshi Ohta
  • ,
  • Chika Yamashiro
  • ,
  • Tomonori Nakamura
  • ,
  • Takuya Yamamoto
  • ,
  • Mitinori Saitou

39
21
開始ページ
e104929
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.15252/embj.2020104929

Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least ~106 -fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.

リンク情報
DOI
https://doi.org/10.15252/embj.2020104929
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32954504
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604613
ID情報
  • DOI : 10.15252/embj.2020104929
  • PubMed ID : 32954504
  • PubMed Central 記事ID : PMC7604613

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