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Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm

Author

Listed:
  • Kazutoshi Takahashi

    (Center for iPS cell Research and Application, Kyoto University)

  • Koji Tanabe

    (Center for iPS cell Research and Application, Kyoto University)

  • Mari Ohnuki

    (Center for iPS cell Research and Application, Kyoto University)

  • Megumi Narita

    (Center for iPS cell Research and Application, Kyoto University)

  • Aki Sasaki

    (Center for iPS cell Research and Application, Kyoto University)

  • Masamichi Yamamoto

    (Development Unit, Gunma University Maebashi)

  • Michiko Nakamura

    (Center for iPS cell Research and Application, Kyoto University)

  • Kenta Sutou

    (Center for iPS cell Research and Application, Kyoto University)

  • Kenji Osafune

    (Center for iPS cell Research and Application, Kyoto University)

  • Shinya Yamanaka

    (Center for iPS cell Research and Application, Kyoto University
    Gladstone Institute of Cardiovascular Disease)

Abstract

During mammalian embryonic development, the primitive streak initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of a handful of transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency. Here we show that during OSKM-induced reprogramming towards pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including mesenchymal to epithelial transition and the activation of late pluripotency markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm.

Suggested Citation

  • Kazutoshi Takahashi & Koji Tanabe & Mari Ohnuki & Megumi Narita & Aki Sasaki & Masamichi Yamamoto & Michiko Nakamura & Kenta Sutou & Kenji Osafune & Shinya Yamanaka, 2014. "Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4678
    DOI: 10.1038/ncomms4678
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    Cited by:

    1. Francesco Panariello & Onelia Gagliano & Camilla Luni & Antonio Grimaldi & Silvia Angiolillo & Wei Qin & Anna Manfredi & Patrizia Annunziata & Shaked Slovin & Lorenzo Vaccaro & Sara Riccardo & Valenti, 2023. "Cellular population dynamics shape the route to human pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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