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

Kazutoshi Takahashi (), Koji Tanabe, Mari Ohnuki, Megumi Narita, Aki Sasaki, Masamichi Yamamoto, Michiko Nakamura, Kenta Sutou, Kenji Osafune and Shinya Yamanaka ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4678

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