Further Characterisation of the Molecular Signature of Quiescent and Activated Mouse Muscle Satellite Cells

Abstract

Satellite cells are the resident stem cells of adult skeletal muscle. To date though, there is a paucity of native markers that can be used to easily identify quiescent satellite cells, with Pax7 probably being the best that is currently available. Here we have further characterized a number of recently described satellite cell markers, and also describe novel ones. Caveolin-1, integrin α7 and the calcitonin receptor proved reliable markers for quiescent satellite cells, being expressed by all satellite cells identified with Pax7. These three markers remained expressed as satellite cells were activated and underwent proliferation. The nuclear envelope proteins lamin A/C and emerin, mutations in which underlie Emery-Dreifuss muscular dystrophy, were also expressed in both quiescent and proliferating satellite cells. Conversely, Jagged-1, a Notch ligand, was not expressed in quiescent satellite cells but was induced upon activation. These findings further contribute to defining the molecular signature of muscle satellite cells.

CD8 T Cells Are Involved in Skeletal Muscle Regeneration through Facilitating MCP-1 Secretion and Gr1high Macrophage Infiltration

“…After ablation of satellite cells, the muscle repair is prevented, and regenerated TA muscle is completely lost 56 d postinjury (37). Previous studies have indicated that Pax7, which is essential for satellite cell specification and survival (38), is maintained in both quiescent and activated satellite cells in adult mouse muscle (39), and the inactivation of Pax7 leads to complete ablation of satellite cells (40), and inhibits skeletal muscle regeneration (37,41). Thus, satellite cells with Pax7 expression are indispensable for skeletal muscle regeneration (36).…”

Are Human and Mouse Satellite Cells Really the Same?

“…Both mouse and human skeletal muscles are capable of regeneration, but whether human satellite cells can self-renew following injury to give rise to functional satellite cells has not been demonstrated. In order to progress work on human satellite cells, one first needs to ascertain whether newly discovered markers of mouse satellite cells Gnocchi et al 2009;Pallafacchina et al 2010) are expressed by human satellite cells. Then, if there was a method to induce cultured mpc to give rise to quiescent satellite cells (e.g., by re-creating the niche in vivo), these markers could be verified and used to either subfractionate human satellite cells or study their activation and differentiative potential in vitro.…”

“…Isolated viable muscle fibers bearing their satellite cells under the basal lamina may be either fixed immediately or placed in suspension culture so that the activation, proliferation, differentiation, and self-renewal of satellite cells in their niche can be followed (Beauchamp et al 2000;Zammit et al 2004;Collins et al 2007Collins et al , 2009Day et al 2007;Gnocchi et al 2009). Fibers may be cultured on a substrate, usually Matrigel (a commercially available mixture of basement membrane components and growth factors), or other substrates, such as collagen (Shefer et al 2004); under these conditions, satellite cells migrate from the fiber, proliferate, and differentiate into myotubes (Rosenblatt et al 1995;Blaveri et al 1999;De Coppi et al 2006;Yablonka-Reuveni and Anderson 2006;Boldrin et al 2007;Malerba et al 2009).…”

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

“…The mRNA expression of genes from muscle fibre associated satellite cells was assessed using previously described protocols (Gnocchi et al, 2009). Briefly, single muscle fibres were stripped of their satellite cells via digestion in 0.125% Trypsin-EDTA at 37˚C for 15 min followed by gentle trituration to release cells.…”