Résumé :
|
Sublaminar location has been the cornerstone of both definition and identification of muscle satellite cells (mSCs), but little attention has been paid to the anatomic organization of the mSC niche, and interplays of mSCs with their neighborhood remains a major unexplored area of mSC biology. It is now clear that most adult mSCs are closely associated with capillaries, and that endothelial cells (ECs) functionally interact with mSCs, likely favoring coordinated angio-myogenesis during myorepair (Christov et al, Mol Biol Cell 2007). Except recent demonstration that muscle capillary mural cells called pericytes may have mesenchymal stem cell potential, the role of this cell type has been poorly investigated in muscle. Pericytes are known to stabilize the endothelial tube through angiopoietin 1 (Ang1)/Tie2 receptor signaling. Similarly to ECs, mSCs express the receptor Tie2 and respond to Ang1/Tie -2 signalling, in terms of growth inhibition, prosurvival effects and self-renewal (Abou Khalil et al, Cell Stem Cell 2009) but the hierarchy among the different local cell sources of Ang1 remains undetermined.Using NG2/CD31 double immunostainings, we first showed that, contrary to the previous literature, the pericyte:EC ratio is high in adult human and mouse muscle (about 90%). 73% of mSC were at less than 5?m from pericytes in adult mouse muscle. 3D imaging showed persistence of a basal lamina in between pericytes and ECs challenging existence of direct cell contacts. During post-natal development, pericytes initially remote from cycling mSCs, progressively move with ECs closer to mSC becoming mitotically quiescent. As this may suggest paracrine communication, we performed in vitro functional studies using co-cultures of human cells in transwell: ECs induced strong mSC growth, whereas pericytes, alone or admixed with ECs, decreased mSC growth. Pericytes also stimulated mSC differentiation into myotubes, with conspicuous persistence of unfused mononuclear cells, presumably reserve cells. ELISA tests on cell supernatants consistently showed 2 fold higher Ang1 production by pericytes compared to mSCs and, unlike ECs, no Ang2 production. In conclusion, pericytes are abundant in adult muscle and play a role in the mSC niche by providing paracrine signaling to mSCs: Ang1 may promote quiescence and self renewal, whereas other, as yet unknown, factors favor differentiation.
|