Extracellular matrix regulation in the muscle satellite cell niche

Abstract

Increasing evidence points to extracellular matrix (ECM) components playing integral roles in regulating the muscle satellite cell (SC) niche. Even small alterations to the niche ECM can have profound effects on SC localization, activation, self-renewal, proliferation and differentiation. This review will focus on the ECM components that comprise the niche, how they are modulated in health and disease and how these changes are thought to affect SC function. Particular emphasis will be placed on the pathological niche and interventions that aim to restore healthy structure and function, as a better understanding of the interplay between the SC and its environment will drive more targeted and effective therapies.

Keywords: Basement membrane; collagen; proteoglycan; satellite cell; stem cell.

Figure 1

Schematic diagram of the satellite cell (SC) niche. SCs reside between the basal lamina (BL) and the muscle fiber sarcolemma where they interact with matrix components of the niche. Through integrins, SCs bind to collagen type IV and laminin. The ECM protein nidogen helps cross-link these two components into a matrix. They in turn bind to collagen type VI and several proteoglycans including perlecan and decorin. Collagen type VI integrates the BL with the reticular lamina composed primarily of collagen types I and III and fibronectin. On the other side of the SC niche, the muscle fiber sarcolemma links to the BL through the dystroglycan complex, which binds to the actin cytoskeleton thorough dystrophin and to laminin in the BL.

Figure 2

Schematic diagrams illustrating some differences between the quiescent, activated and aged satellite cell (SC) niche. (Far left) The quiescent SC senses the stiffness of its niche through integrins and expresses various matrix proteins to maintain its extracellular matrix (ECM). Within this matrix, growth factors and signaling molecules such as Wnts and TGF-β are sequestered, maintaining the “quiet” state. (Center) In response to injury, components of the basal lamina are degraded by matrix proteases which results in the release of signaling molecules that play a role in activation and proliferation of the SC. The activated SC divides and some daughter cells begin to differentiate. (Far right) In the aged niche, matrix components accumulate to form a denser and thicker basal lamina. The stiffness sensing and sequestration of signaling molecules may be affected by this change.