Loss of Ptpn11 (Shp2) drives satellite cells into quiescence

Abstract
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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.

Data availability

The following data sets were generated

1. Griger J
(2017) Genome wide expression analysis of FACS-isolated Shp2 mutant neonatal myogenic progenitor cells
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE97430).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97430

Article and author information

Author details

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.
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.
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.
Verena Schöwel

Muscle Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Charles Keller

Children's Cancer Therapy Development Institute, Beaverton, United States

Competing interests
The authors declare that no competing interests exist.
Simone Spuler

Muscle Research Unit, Experimental and Clinical Research Center, Charité, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0155-1117
Marc Nazaré

Medicinal Chemistry, Leibniz Institute for Molecular Pharmacology, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.