論文

査読有り
2017年8月

Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation

NATURE
  • Masaki Yagi
  • ,
  • Satoshi Kishigami
  • ,
  • Akito Tanaka
  • ,
  • Katsunori Semi
  • ,
  • Eiji Mizutani
  • ,
  • Sayaka Wakayama
  • ,
  • Teruhiko Wakayama
  • ,
  • Takuya Yamamoto
  • ,
  • Yasuhiro Yamada

548
7666
開始ページ
224
終了ページ
+
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/nature23286
出版者・発行元
NATURE PUBLISHING GROUP

Inhibitors of Mek1/2 and Gsk3 beta, known as 2i, enhance the derivation of embryonic stem (ES) cells and promote ground-state pluripotency in rodents(1,2). Here we show that the derivation of female mouse ES cells in the presence of 2i and leukaemia inhibitory factor (2i/L ES cells) results in a widespread loss of DNA methylation, including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, early-passage 2i/L ES cells efficiently differentiate into somatic cells, and this process requires genome-wide de novo DNA methylation. However, the majority of imprinting control regions (ICRs) remain unmethylated in 2i/L-ES-cell-derived differentiated cells. Consistently, 2i/L ES cells exhibit impaired autonomous embryonic and placental development by tetraploid embryo complementation or nuclear transplantation. We identified the derivation conditions of female ES cells that display 2i/L-ES-cell-like transcriptional signatures while preserving gamete-derived DNA methylation and autonomous developmental potential. Upon prolonged culture, however, female ES cells exhibited ICR demethylation regardless of culture conditions. Our results provide insights into the derivation of female ES cells reminiscent of the inner cell mass of preimplantation embryos.

Web of Science ® 被引用回数 : 93

リンク情報
DOI
https://doi.org/10.1038/nature23286
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28746308
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000407284300046&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/nature23286
  • ISSN : 0028-0836
  • eISSN : 1476-4687
  • PubMed ID : 28746308
  • Web of Science ID : WOS:000407284300046

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