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Foxd1 is a mediator and indicator of the cell reprogramming process

Author

Listed:
  • Makito Koga

    (RIKEN Center for Developmental Biology
    Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    Graduate School of Biostudies, Kyoto University)

  • Mitsuhiro Matsuda

    (RIKEN Center for Developmental Biology
    Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    Graduate School of Biostudies, Kyoto University)

  • Teruhisa Kawamura

    (Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    College of Life Sciences, Ritsumeikan University)

  • Takahiro Sogo

    (Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    Kyoto Medical Center, National Hospital Organization)

  • Asako Shigeno

    (Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    College of Life Sciences, Ritsumeikan University)

  • Eisuke Nishida

    (Graduate School of Biostudies, Kyoto University
    JST, CREST)

  • Miki Ebisuya

    (RIKEN Center for Developmental Biology
    Career-Path Promotion Unit for Young Life Scientists, Kyoto University
    JST, CREST)

Abstract

It remains unclear how changes in gene expression profiles that establish a pluripotent state are induced during cell reprogramming. Here we identify two forkhead box transcription factors, Foxd1 and Foxo1, as mediators of gene expression programme changes during reprogramming. Knockdown of Foxd1 or Foxo1 reduces the number of iPSCs, and the double knockdown further reduces it. Knockout of Foxd1 inhibits downstream transcriptional events, including the expression of Dax1, a component of the autoregulatory network for maintaining pluripotency. Interestingly, the expression level of Foxd1 is transiently increased in a small population of cells in the middle stage of reprogramming. The transient Foxd1 upregulation in this stage is correlated with a future cell fate as iPSCs. Fate mapping analyses further reveal that >95% of iPSC colonies are derived from the Foxd1-positive cells. Thus, Foxd1 is a mediator and indicator of successful progression of reprogramming.

Suggested Citation

  • Makito Koga & Mitsuhiro Matsuda & Teruhisa Kawamura & Takahiro Sogo & Asako Shigeno & Eisuke Nishida & Miki Ebisuya, 2014. "Foxd1 is a mediator and indicator of the cell reprogramming process," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4197
    DOI: 10.1038/ncomms4197
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