論文

査読有り
2017年7月

In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate

EMBO JOURNAL
  • Hiroshi Ohta
  • ,
  • Kazuki Kurimoto
  • ,
  • Ikuhiro Okamoto
  • ,
  • Tomonori Nakamura
  • ,
  • Yukihiro Yabuta
  • ,
  • Hidetaka Miyauchi
  • ,
  • Takuya Yamamoto
  • ,
  • Yukiko Okuno
  • ,
  • Masatoshi Hagiwara
  • ,
  • Kenjiro Shirane
  • ,
  • Hiroyuki Sasaki
  • ,
  • Mitinori Saitou

36
13
開始ページ
1888
終了ページ
1907
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.15252/embj.201695862
出版者・発行元
WILEY

The expansion of primordial germ cells (PGCs), the precursors for the oocytes and spermatozoa, is a key challenge in reproductive biology/medicine. Using a chemical screening exploiting PGC-like cells (PGCLCs) induced from mouse embryonic stem cells (ESCs), we here identify key signaling pathways critical for PGCLC proliferation. We show that the combinatorial application of Forskolin and Rolipram, which stimulate cAMP signaling via different mechanisms, expands PGCLCs up to similar to 50-fold in culture. The expanded PGCLCs maintain robust capacity for spermatogenesis, rescuing the fertility of infertile mice. Strikingly, during expansion, PGCLCs comprehensively erase their DNA methylome, including parental imprints, in a manner that precisely recapitulates genome-wide DNA demethylation in gonadal germ cells, while essentially maintaining their identity as sexually uncommitted PGCs, apparently through appropriate histone modifications. By establishing a paradigm for PGCLC expansion, our system reconstitutes the epigenetic "blank slate" of the germ line, an immediate precursory state for sexually dimorphic differentiation.

Web of Science ® 被引用回数 : 33

リンク情報
DOI
https://doi.org/10.15252/embj.201695862
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28559416
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000404566600008&DestApp=WOS_CPL
ID情報
  • DOI : 10.15252/embj.201695862
  • ISSN : 0261-4189
  • eISSN : 1460-2075
  • ORCIDのPut Code : 34188781
  • PubMed ID : 28559416
  • Web of Science ID : WOS:000404566600008

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