Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells

Toshie Shinagawa, Tsuyoshi Takagi, Daisuke Tsukamoto, Chinatsu Tomaru, Linh My Huynh, Padavattan Sivaraman, Thirumananseri Kumarevel, Kimiko Inoue, Ryuichiro Nakato, Yuki Katou, Takashi Sado, Satoru Takahashi, Atsuo Ogura, Katsuhiko Shirahige, Shunsuke Ishii

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Expression of Oct3/4, Sox2, Klf4, and c-Myc (OSKM) can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Somatic cell nuclear transfer (SCNT) can also be used for reprogramming, suggesting that factors present in oocytes could potentially augment OSKM-mediated induction of pluripotency. Here, we report that two histone variants, TH2A and TH2B, which are highly expressed in oocytes and contribute to activation of the paternal genome after fertilization, enhance OSKM-dependent generation of iPSCs and can induce reprogramming with Klf4 and Oct3/4 alone. TH2A and TH2B are enriched on the X chromosome during the reprogramming process, and their expression in somatic cells increases the DNase I sensitivity of chromatin. In addition, Xist deficiency, which was reported to enhance SCNT reprogramming efficiency, stimulates iPSC generation using TH2A/TH2B in conjunction with OSKM, but not OSKM alone. Thus, TH2A/TH2B may enhance reprogramming by introducing processes that normally operate in zygotes and during SCNT.

Original languageEnglish
Pages (from-to)217-27
Number of pages11
JournalCell Stem Cell
Issue number2
Publication statusPublished - 6 Feb 2014

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cellular Reprogramming
  • Chromatin
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Genome
  • Histones
  • Induced Pluripotent Stem Cells
  • Mice
  • Oocytes
  • Protein Isoforms
  • RNA, Messenger
  • X Chromosome
  • Journal Article


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