Skeletal muscle stem cells in comfort and stress

The satellite cell and stromal cell niche. Satellite cells states are regulated through their interactions with their microenvironment. While direct interactions (M-cadherin, Notch pathway)38,46 and communication (FGF2-FGFR1 pathway)48 between muscle fibres and satellite cells have been identified, muscle stem cells also interact with a variety of components of the extracellular matrix (e.g. Collagens VI and V, Laminin, Fibronectin, SDC3/4)45,79 and diffusable cytokines and growth factors (e.g. Angiopoietin-Tie2 receptor)37. In addition to satellite cells, several cell types contribute to muscle growth, homoeostasis and regeneration, including pericytes, mesenchymal stromal cells (e.g. Pw1+ Interstitial Cells, FibroAdipogenic Progenitors, Twist2+ cells)16,19,21, immune cells (e.g. resident or infiltrating macrophages)156 as well as connective tissue cells. These interactions are remodelled during ageing, notably with increased FGF2 production from muscle fibres and decreased expression of FGFR1 in satellite cells, driving satellite cells to break quiescence39, and decreased levels of fibronectin45, which weakens satellite cell adhesion capacity and increases their susceptibility to apoptosis by anoiki