PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells

Masashi Yamaji, Jun Ueda, Katsuhiko Hayashi, Hiroshi Ohta, Yukihiro Yabuta, Kazuki Kurimoto, Ryuichiro Nakato, Yasuhiro Yamada, Katsuhiko Shirahige, Mitinori Saitou

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.

Original languageEnglish
Pages (from-to)368-382
Number of pages15
JournalCell stem cell
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 7 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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  • Cite this

    Yamaji, M., Ueda, J., Hayashi, K., Ohta, H., Yabuta, Y., Kurimoto, K., Nakato, R., Yamada, Y., Shirahige, K., & Saitou, M. (2013). PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell stem cell, 12(3), 368-382. https://doi.org/10.1016/j.stem.2012.12.012