Résumé :
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Understanding how stem cell niches are organized in vivo and what interactions their progeny develop with neighbouring cell types is a critical issue in stem cell biology. Sublaminar location led to identification of muscle satellite cells (SCs), but little is known about the anatomical organization of the sublaminal niche surroundings. Moreover, signals that are likely conferred to myogenic cells by either direct contacts with the adjacent myofiber or soluble factors released by neighbouring non-muscle cells, constitute one of the major unexplored areas of SC biology. As different types of adult stem/progenitor cells crucially interact with the microvascular bed, we examined if the microvascular bed could constitute a partner of SCs. Genetically engineered mice (Myf5nLacZ/+, Myf5GFP-P/+) allowing direct 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 anatomic stability of juxtavascular SC niches. BrdU pulse-chase experiments also localise quiescent and less quiescent SCs near vessels. SCs, and to a lesser extent myonuclei, were non-randomly associated with capillaries in humans. Significantly, they were linearly correlated with capillarization of myofibers, regardless to their type, in normal muscle. They also varied in paradigmatic physiologic and pathologic 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. To contact the author:: romain.gherardi@hmn.aphp.fr.
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