Blood vessels and the satellite cell niche.

The fate of stem cell is regulated by cues received from the surrounding area. Recently, the concept of "stem cell zone"--rather than a predefined niche--introduced the notion of dynamic and permanent interactions between stem cells and their microenvironment. In adult skeletal muscle, satellite cells are considered as the main stem cells responsible for muscle repair and maintenance. They are localized close to vessels regardless their state of activation and differentiation. Moreover, the number of satellite cells is positively correlated to the capillarization of the myofiber. Angiogenesis has been known for a long time to be essential for muscle repair. However, relationships between vessel cells and satellite/myogenic cells that govern myogenic cell expansion, myogenesis, and angiogenesis have been only recently investigated. In this chapter, we discuss the possible existence of a vascular amplifying/differentiating niche, in an attempt to reconciliate several recent observations showing that satellite/myogenic cells interact with various cell types during the time course of muscle regeneration. Indeed, endothelial cells (ECs) stimulate myogenic cell growth and, inversely, differentiating myogenic cells promote angiogenesis. However, stromal cells may also provide some proliferating or differentiating cues to satellite/myogenic cells in this vascular area. Although some molecular effectors have been identified, including growth factors and cytokines, molecular regulations that occur within this vascular amplifying/differentiating niche requires further investigation. At the end of muscle repair, maturation of newly formed vessels takes place. In this context, we discuss the potential quiescence niche of satellite cells and the specific role of periendothelial cells. Indeed, periendothelial cells promote the return to quiescence of a subset of satellite/myogenic cells and maintain their quiescence (through Angiopoietin-1/Tie-2 signaling). We ask to what extent the environment may control the fate choice of satellite/myogenic cells and we also question the "hypoxic niche" in skeletal muscle, such a quiescence niche having being observed in the bone marrow.