1. Stem Cells and Regenerative Medicine
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Distinct SoxB1 networks are required for naive and primed pluripotency

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Cite this article as: eLife 2017;6:e27746 doi: 10.7554/eLife.27746

Abstract

Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.

Article and author information

Author details

  1. Andrea Corsinotti

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Frederick CK Wong

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Tülin Tatar

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Iwona Szczerbinska

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Florian Halbritter

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2452-4784
  6. Douglas Colby

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Sabine Gogolok

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Raphaël Pantier

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Kirsten Liggat

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Elham S Mirfazeli

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Elisa Hall-Ponsele

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicholas P Mullin

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Valerie Wilson

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    v.wilson@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4182-5159
  14. Ian Chambers

    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    ichambers@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2605-1597

Funding

Medical Research Council

  • Andrea Corsinotti
  • Frederick CK Wong
  • Florian Halbritter
  • Douglas Colby
  • Nicholas P Mullin
  • Valerie Wilson
  • Ian Chambers

Biotechnology and Biological Sciences Research Council

  • Elisa Hall-Ponsele
  • Ian Chambers

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experiments were performed under the UK Home Office project license PPL60/4435, approved by the Animal Welfare and Ethical Review Panel of the MRC Centre for Regenerative Medicine and within the conditions of the Animals (Scientific Procedures) Act 1986.

Reviewing Editor

  1. Martin Pera, University of Melbourne, Australia

Publication history

  1. Received: May 9, 2017
  2. Accepted: December 18, 2017
  3. Accepted Manuscript published: December 19, 2017 (version 1)
  4. Version of Record published: January 8, 2018 (version 2)

Copyright

© 2017, Corsinotti 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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