Loss of Ptpn11 (Shp2) drives satellite cells into quiescence.
Joscha GrigerRobin SchneiderInes LahmannVerena SchöwelCharles KellerSimone SpulerMarc NazareCarmen BirchmeierPublished in: eLife (2017)
The equilibrium between proliferation and quiescence of myogenic progenitor and stem cells is tightly regulated to ensure appropriate skeletal 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.
Keyphrases
- stem cells
- skeletal muscle
- cell cycle
- cell proliferation
- growth factor
- cell therapy
- resting state
- insulin resistance
- preterm infants
- functional connectivity
- dna methylation
- single cell
- signaling pathway
- induced apoptosis
- mesenchymal stem cells
- oxidative stress
- genome wide
- cell cycle arrest
- molecular dynamics
- adipose tissue
- big data
- high fat diet induced
- artificial intelligence
- pi k akt
- free survival
- single molecule
- protein kinase