1. Developmental Biology
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Loss of Ptpn11 (Shp2) drives satellite cells into quiescence

  1. Joscha Griger
  2. Robin Schneider
  3. Ines Lahmann
  4. Verena Schöwel
  5. Charles Keller
  6. Simone Spuler
  7. Marc Nazaré
  8. Carmen Birchmeier  Is a corresponding author
  1. Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Germany
  2. Charité, Germany
  3. Children's Cancer Therapy Development Institute, United States
  4. Leibniz Institute for Molecular Pharmacology, Germany
Research Article
  • Cited 5
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Cite this article as: eLife 2017;6:e21552 doi: 10.7554/eLife.21552

Abstract

The equilibrium between proliferation and quiescence of myogenic progenitor and stem cells is tightly regulated to ensure appropriate muscle growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an important transducer of growth factor and cytokine signals. Here we combined complex genetic analyses, biochemical studies and pharmacological interference to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss of Ptpn11 drove muscle stem cells out of the proliferative and into a resting state during muscle growth. This Ptpn11 function was observed in postnatal but not fetal myogenic stem cells. Furthermore, muscle repair was severely perturbed when Ptpn11 was ablated in stem cells due to a deficit in stem cell proliferation and survival. Our data demonstrate a molecular difference in the control of cell cycle withdrawal in fetal and postnatal myogenic stem cells, and assign to Ptpn11 signaling a key function in satellite cell activity.

Article and author information

Author details

  1. Joscha Griger

    Developmental Biology/Signal Transduction Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Robin Schneider

    Developmental Biology/Signal Transduction Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ines Lahmann

    Developmental Biology/Signal Transduction Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Verena Schöwel

    Muscle Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Charles Keller

    Children's Cancer Therapy Development Institute, Beaverton, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Simone Spuler

    Muscle Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0155-1117
  7. Marc Nazaré

    Medicinal Chemistry, Leibniz Institute for Molecular Pharmacology, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Carmen Birchmeier

    Developmental Biology/Signal Transduction Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Berlin, Germany
    For correspondence
    cbirch@mdc-berlin.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2041-8872

Funding

Deutsche Forschungsgemeinschaft (Graduate student fellowship)

  • Joscha Griger

Deutsche Forschungsgemeinschaft (KFO192)

  • Simone Spuler
  • Carmen Birchmeier

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

Ethics

Animal experimentation: All procedures involving animals and their care were carried out in accordance with the guidelines for animal experiments at the Max-Delbrueck-Center (MDC), which conform to the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, revised 1996), the European Parliament Directive 2010/63/EU and the 22 September 2010 Council on the protection of animals. Animal experimentation was approved by the local Ethics committee for animal experiments at the Landesamt fÃ1/4r Gesundheit und Soziales (GO130/13; G0028/14). The animal house at the MDC is registered according to paragraph11 German Animal Welfare Law.

Reviewing Editor

  1. Margaret Buckingham, Institut Pasteur, France

Publication history

  1. Received: September 14, 2016
  2. Accepted: April 29, 2017
  3. Accepted Manuscript published: May 2, 2017 (version 1)
  4. Version of Record published: May 23, 2017 (version 2)

Copyright

© 2017, Griger 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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