A tale of two niches: differential functions for VCAM-1 in satellite cells under basal and injured conditions

Abstract

Cell-cell adhesion molecules play key roles in maintaining quiescence or promoting activation of various stem cells in their niche. Muscle stem cells called satellite cells (SC) are critical for skeletal muscle regeneration after injury, but little is known about the role of adhesion molecules in regulating the behavior of these stem cells. Vascular cell adhesion molecule-1 (VCAM-1) is a cell-cell adhesion protein expressed on quiescent and activated SC whose function is unknown in this context. We deleted from SC using an inducible Cre recombinase in young mice. In the injured niche, SC underwent premature lineage progression to a more differentiated state as well as apoptosis leading to a transient delay in myofiber growth during regeneration. Apoptosis was also increased in SC in vitro concomitant with decreased levels of phosphorylated Akt, a prosurvival signal activated by VCAM-1 signaling in other cell types. During muscle regeneration, we observed an influx of immune cells expressing α4 integrin, a component of the major, high-affinity VCAM-1 ligand, α4β1 integrin. Furthermore, α4 integrin mRNA and protein were induced in SC 2 days after injury. These results suggest that SC interact with other SC as well as immune cells through α4β1 integrin in the injured niche to promote expansion of SC. In the uninjured niche, multiple cell types also expressed α4 integrin. However, only basal fusion of SC with myofibers was decreased, contributing to decreased myofiber growth. These studies define differential roles for VCAM-1 in SC depending on the state of their niche.

Optimising platelet secretomes to deliver robust tissue‐specific regeneration

“…Our data on the composition of platelet releasate revealed that known key growth factors driving myoblast and/or chondrocyte proliferation such as PDGFBB and VEGFA were increased several fold in SR (Kieswetter, Schwartz, Alderete, Dean, & Boyan, ; Scully, Sfyri, et al, ). VCAM‐1 was previously shown to increase cardiomyocyte proliferation and skeletal myoblast differentiation and was 3.8‐fold more abundant in SR compared with physiological releasate (Choo, Canner, Vest, Thompson, & Pavlath, ; Iwamiya, Matsuura, Masuda, Shimizu, & Okano, ). Similarly, growth factors driving fibroblast proliferation such as EGF and FGF‐2 were increased 1.92‐ and 3.43‐fold, respectively (Yu, Matsuda, Takeda, Uchinuma, & Kuroyanagi, ).…”

Persistent COUP-TFII expression underlies the myopathy and impaired muscle regeneration observed in resistance to thyroid hormone-alpha

“…Even if Integrin α7β1 is initially highly expressed in differentiated myotube, a switch in integrin signature is needed for proper myoblast proliferation and differentiation 24 . Itgα4 expression is induced in SC right after skeletal muscle injury to promote SCs’ activation and proliferation 25 , while Itgα5, has a crucial role in SCs’ migration and adhesion 26 .…”

Isolation of muscle stem cells from rat skeletal muscles

“…CD106 is a trans-membrane protein in the immunoglobulin superfamily that has been successfully used for isolation of mouse MuSCs ( Liu et al, 2015 ). Importantly, expression of this protein in quiescent cells is required for maintenance of their basal function and prevention of premature lineage progression ( Choo et al, 2017 ). The current study demonstrates, for the first time, that CD106 is a reliable marker for the isolation of a highly enriched MuSC population from various rat skeletal muscles.…”