Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence

Abstract

The satellite cells, which serve as adult muscle stem cells, are both located beneath myofiber basement membranes and closely associated with capillary endothelial cells. We observed that 90% of capillaries were associated with pericytes in adult mouse and human muscle. During post-natal growth, newly formed vessels with their neuroglial 2 proteoglycan (NG2)-positive pericytes became progressively associated with the post-natal muscle stem cells, as myofibers increased in size and satellite cells entered into quiescence. In vitro, human muscle-derived pericytes promoted myogenic cell differentiation through insulin-like growth factor 1 (IGF1) and myogenic cell quiescence through angiopoietin 1 (ANGPT1). Diphtheria toxin-induced ablation of muscle pericytes in growing mice led both to myofiber hypotrophy and to impaired establishment of stem cells quiescence. Similar effects were observed following conditional in vivo deletion of pericyte Igf1 and Angpt1 genes, respectively. Our data therefore demonstrate that, by promoting post-natal myogenesis and stem cell quiescence, pericytes play a key role in the microvascular niche of satellite cells.

Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development

“…In vivo analysis indicated that the inhibition of TGFβ2 could downregulate the expression of PAX7 and promote the regeneration of skeletal muscles. Previous studies indicated that the activation of quiescent satellite cells was accompanied by reduced PAX7 and increased MYOD (Kostallari et al., 2015; Sato et al., 2014). The overexpression of TGFβ2 and TGFβ3 can decrease the myogenic differentiation of myoblasts (de Mello, Streit, Sabin & Gabillard, 2015; Schabort, van der Merwe & Niesler, 2011).…”

Distinct Embryonic and Adult Fates of Multipotent Myogenic Progenitors Isolated from Skeletal Muscle and Bone Marrow

“…The rarity and lack of a physiological role to postnatal muscle tissue suggest the potential identity of NEMPs as embryonic remnants. This character distinguish NEMPs from subpopulations of muscle satellite cells [16][17][18]43], or muscle-derived pericytes and interstitial progenitors [44][45][46], which are relative abundance in tissue (hundreds or thousands of sorted cells per 100 mg muscle), and functionally related to postnatal muscle, vasculature or connective tissues. However, whether NEMPs exist in some of the muscle-based cell cultures is unknown, and their potential impact on the biological behaviors of these cells needs to be established.…”

Regulation and phylogeny of skeletal muscle regeneration

“…Pericytes are located peripheral to the endothelium of microvessels and are involved in blood vessel growth, remodelling, homeostasis, and permeability (Armulik et al, 2011). Pericytes in skeletal muscles are constituents of the satellite cell niche where they secrete molecules such as IGF1 (insulin growth factor-1) or ANGPT1 (angiopoetin-1) to modulate their behaviour but also postnatal myofibres growth and satellite cell entry in quiescence (Kostallari et al, 2015). After muscle injury, pericytes activate and give rise to a subset of vessel-associated progenitors called mesoangioblasts when isolated from the tissue.…”

“…Originally isolated from the embryonic dorsal aorta, pericytes and mesoangioblasts of skeletal muscle were found to express similar markers (Dellavalle et al, 2011;Dellavalle et al, 2007;Kostallari et al, 2015). Mesoangioblasts have a lower myogenic potential compared to MuSCs however, they expand, migrate and extravasate upon arterial delivery in dystrophic murine and canine models, resulting in increased engraftment efficiency and improved muscle function (Berry et al, 2007;Diaz-Manera et al, 2010;Sampaolesi et al, 2006).…”