Genetically engineered mice (Myf5 nLacZ/؉ , Myf5GFP-P/؉ ) allowing direct muscle satellite cell (SC) visualization indicate that, in addition to being located beneath myofiber basal laminae, SCs are strikingly close to capillaries. After GFP ؉ bone marrow transplantation, blood-borne cells occupying SC niches previously depleted by irradiation were similarly detected near vessels, thereby corroborating the anatomical stability of juxtavascular SC niches. Bromodeoxyuridine pulse-chase experiments also localize quiescent and less quiescent SCs near vessels. SCs, and to a lesser extent myonuclei, were nonrandomly associated with capillaries in humans. Significantly, they were correlated with capillarization of myofibers, regardless to their type, in normal muscle. They also varied in paradigmatic physiological and pathological situations associated with variations of capillary density, including amyopathic dermatomyositis, a unique condition in which muscle capillary loss occurs without myofiber damage, and in athletes in whom capillaries increase in number. Endothelial cell (EC) cultures specifically enhanced SC growth, through IGF-1, HGF, bFGF, PDGF-BB, and VEGF, and, accordingly, cycling SCs remained mainly juxtavascular. Conversely, differentiating myogenic cells were both proangiogenic in vitro and spatiotemporally associated with neoangiogenesis in muscular dystrophy. Thus, SCs are largely juxtavascular and reciprocally interact with ECs during differentiation to support angio-myogenesis. INTRODUCTIONMuscle tissue repair is a complex biological process that crucially involves activation of stem cells. Skeletal muscle contains two different stem cell types: 1) myogenic stem cells, so-called satellite cells (SCs), that reside beneath the basal lamina of muscle fibers (Mauro, 1961) and express both NCAM/CD56 and early myogenic cell markers such as M-cadherin, Pax7, and Myf5 (Beauchamp et al., 2000;Seale et al., 2000;Hawke and Garry, 2001; Bischoff and FranziniArmstrong, 2004) and 2) interstitial multipotent stem cells, which are extralaminal, exhibit fibroblastic morphology and do not express myogenic markers (Asakura et al., 2001;Tamaki et al., 2002). SCs are primarily quiescent in skeletal muscle, can self-renew (Collins et al., 2005) and upon activation, proliferate and further differentiate to become fusioncompetent myoblasts and ensure muscle regeneration (Hawke and Garry, 2001;Bischoff and Franzini-Armstrong, 2004). Interstitial "muscle-derived" stem cells give rise to several lineages after transplantation and in this setting, contribute to synchronized reconstitution of blood vessels (pericytes, smooth muscle cells [SMCs], and endothelial cells), peripheral nerve (Schwann cells), and muscle cells (myofibers and SCs; Tamaki et al., 2005). However, participation of multipotent interstitial stem cells in physiological muscle repair appears to be limited. Instead, it is widely accepted that sublaminal SCs represent the pre-eminent muscle stem cell type used for muscle growth, repair and regeneration (Dhawan...