Cell-cell contact and signaling in the muscle stem cell niche

Abstract

Muscle stem cells (also called satellite cells or SCs) rely on their local niche for regulatory signals during homeostasis and regeneration. While a number of cell types communicate indirectly through secreted factors, here we focus on the significance of direct contact between SCs and their neighbors. During quiescence, SCs reside under a basal lamina and receive quiescence-promoting signals from their adjacent skeletal myofibers. Upon injury, the composition of the niche changes substantially, enabling the formation of new contacts that mediate proliferation, self-renewal, and differentiation. In this review, we summarize the latest work in understanding cell-cell contact within the satellite cell niche and highlight areas of open questions for future studies.

Keywords: Cadherin; Cell adhesion; Muscle stem cell; Notch pathway; Satellite cell; Skeletal muscle; Stem cell niche.

Figure 1.. The quiescent satellite cell niche.

Quiescent satellite cells (QSCs) reside between multinucleated myofibers and a surrounding basal lamina. QSCs adhere to the basal lamina through integrins (not shown), and mediate contact with myofibers through classical cadherins and Notch receptor-ligand interactions. Other niche cells (such as tissue-specific macrophages) are housed within an interstitial matrix, separated from QSCs. Blood vessels that make up the niche vasculature are found in close proximity to QSCs but have not been shown to penetrate through the basal lamina to form stable cell-cell contacts with SCs or myofibers. Various cells are not drawn to scale.

Figure 2.. The regenerating satellite cell niche.

following muscle injury, damage to the niche enables the formation of new cell-cell contacts during regeneration. Perturbation of the basal lamina allows macrophages to interact with activated SCs through VCAM-1 and VLA-4. Proliferating, activated SCs communicate with each other through M-cadherin and Dll1/Notch 2 signaling, and activated SCs signal to their adjacent myofibers through Ephrin/Eph ligand-receptor interactions.