1. Developmental Biology and Stem Cells
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The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways

  1. Qingqing Zhu
  2. Lu Song
  3. Guangdun Peng
  4. Na Sun
  5. Jun Chen
  6. Ting Zhang
  7. Nengyin Sheng
  8. Wei Tang
  9. Cheng Qian
  10. Yunbo Qiao
  11. Ke Tang
  12. Jing-Dong J Han
  13. Jinsong Li
  14. Naihe Jing Is a corresponding author
  1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
  2. CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
  3. Institute of Life Science, Nanchang University, China
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Cite as: eLife 2014;3:e02224 doi: 10.7554/eLife.02224

Abstract

The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors. However, how these two events are integrated to ensure appropriate neural conversion remains unclear. Here, we showed that Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown leads to a markedly decreased incorporation of ESCs in the neuroectoderm. By contrast, Pou3f1-overexpressing ESC derivatives preferentially contribute to the neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses indicated that Pou3f1 is an upstream activator of neural lineage genes, and also is a repressor of BMP and Wnt signaling. Our results established that Pou3f1 promotes the neural fate commitment of pluripotent stem cells through a dual role, activating internal neural induction programs and antagonizing extrinsic neural inhibitory signals.

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Author details

  1. Qingqing Zhu

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Lu Song

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Guangdun Peng

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Na Sun

    1. CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Jun Chen

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ting Zhang

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Nengyin Sheng

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Wei Tang

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Cheng Qian

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yunbo Qiao

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Ke Tang

    1. Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Jing-Dong J Han

    1. CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Jinsong Li

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Naihe Jing

    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    1. njing@sibcb.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance under the ethical guidelines of the Institute of Biochemistry and Cell Biology and all experiments were approved by the committee on the Ethics of Animal Experiments of the Shanghai Institute of Biochemistry and Cell Biology.

Reviewing Editor

  1. Hideyuki Okano, Reviewing Editor, Keio University School of Medicine, Japan

Publication history

  1. Received: January 7, 2014
  2. Accepted: June 12, 2014
  3. Accepted Manuscript published: June 14, 2014 (version 1)
  4. Version of Record published: July 15, 2014 (version 2)

Copyright

© 2014, Zhu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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