Biomechanical Origins of Muscle Stem Cell Signal Transduction

• Satellite cells are required to reconstruct skeletal muscle following tissue insult.
• A mechanistic comprehension of satellite cell regulation is still in its nascence.
• Soluble cues can synergize with biophysical niche features to direct stem cell fate.
• An emerging vision of satellite cell biophysical regulation is reviewed.

Skeletal muscle, the most abundant and widespread tissue in the human body, contracts upon receiving electrochemical signals from the nervous system to support essential functions such as thermoregulation, limb movement, blinking, swallowing and breathing. Reconstruction of adult muscle tissue relies on a pool of mononucleate, resident muscle stem cells, known as “satellite cells”, expressing the paired-box transcription factor Pax7 necessary for their specification during embryonic development and long-term maintenance during adult life. Satellite cells are located around the myofibres in a niche at the interface of the basal lamina and the host fibre plasma membrane (i.e., sarcolemma), at a very low frequency. Upon damage to the myofibres, quiescent satellite cells are activated and give rise to a population of transient amplifying myogenic progenitor cells, which eventually exit the cell cycle permanently and fuse to form new myofibres and regenerate the tissue. A subpopulation of satellite cells self-renew and repopulate the niche, poised to respond to future demands. Harnessing the potential of satellite cells relies on a complete understanding of the molecular mechanisms guiding their regulation in vivo. Over the past several decades, studies revealed many signal transduction pathways responsible for satellite cell fate decisions, but the niche cues driving the activation and silencing of these pathways are less clear. Here we explore the scintillating possibility that considering the dynamic changes in the biophysical properties of the skeletal muscle, namely stiffness, and the stretch and shear forces to which a myofibre can be subjected to may provide missing information necessary to gain a full understanding of satellite cell niche regulation.

Biomechanical origins of satellite cell signal transduction. Satellite cells, adult stem cells residing at a low frequency within skeletal muscle tissue, are exposed to dynamic physical cues in the homeostatic and regenerating niche such as extracellular matrix stiffness and may even be subjected to mechanical loading in the form of tensile strain or shear stress.Figure optionsDownload high-quality image (317 K)Download as PowerPoint slide