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The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog

Author

Listed:
  • Jiali Jin

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Jian Liu

    (Chinese Academy of Sciences Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Cong Chen

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Zhenping Liu

    (Shanghai Tenth People’s Hospital of Tongji University, School of Life Science and Technology, Tongji University)

  • Cong Jiang

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Hongshang Chu

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Weijuan Pan

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Xinbo Wang

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University)

  • Lingqiang Zhang

    (State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine)

  • Bin Li

    (Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Cizhong Jiang

    (Shanghai Tenth People’s Hospital of Tongji University, School of Life Science and Technology, Tongji University)

  • Xin Ge

    (Shanghai Tenth People's Hospital of Tongji University, Tongji University)

  • Xin Xie

    (Chinese Academy of Sciences Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ping Wang

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
    Shanghai Tenth People’s Hospital of Tongji University, School of Life Science and Technology, Tongji University)

Abstract

Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency. USP21 is a transcriptional target of the LIF/STAT3 pathway and is downregulated upon differentiation. Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation. In addition, USP21 is recruited to gene promoters by Nanog to deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene expression. Together, our findings provide a regulatory mechanism by which extrinsic signals regulate mESC fate via deubiquitinating Nanog.

Suggested Citation

  • Jiali Jin & Jian Liu & Cong Chen & Zhenping Liu & Cong Jiang & Hongshang Chu & Weijuan Pan & Xinbo Wang & Lingqiang Zhang & Bin Li & Cizhong Jiang & Xin Ge & Xin Xie & Ping Wang, 2016. "The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13594
    DOI: 10.1038/ncomms13594
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