Fig. 1

Living outside the comfort zone: quiescent MuSCs adapt to cellular and environmental stress. A stylised MuSC (green) highlighted over the skeletal muscle myofibres (grey). MuSCs maintain low levels of protein synthesis by phosphorylation of eIF2α and TSC1 inhibition of mTORC1 activity. Genetic inactivation of these stress response pathways in MuSCs leads to G_alert or spontaneous activation. P-eIF2α leads to the assembly of DDX6(+) RNA granules (orange) in MuSCs, which resemble stress granules and may functionally serve as sights of mRNA sequestration. P-eIF2α also leads to translational reprogramming of mRNAs that confer stem cell properties on quiescent, self-renewing, or expanding MuSCs. In the nucleus of quiescent MuSCs (light green), elevated DNA-PKcs levels ensure efficient and accurate DNA repair. Expression of the paired homeodomain transcription factor Pax3 marks a subset of MuSCs with increased resistance to multiple stresses, including DNA damage and environmental pollutants. MuSCs that do not express Pax3 spontaneously activate when challenged with the environmental pollutant TCDD. Quiescent MuSCs express mRNAs for heat shock proteins Hsp40, Hsp70, and Hsp90 (brown) and upregulate these chaperones during early activation. These chaperones may be required to counteract the accumulation of misfolded proteins