Skeletal Myogenic Progenitors Originating from Embryonic Dorsal Aorta Coexpress Endothelial and Myogenic Markers and Contribute to Postnatal Muscle Growth and Regeneration

Abstract

Skeletal muscle in vertebrates is derived from somites, epithelial structures of the paraxial mesoderm, yet many unrelated reports describe the occasional appearance of myogenic cells from tissues of nonsomite origin, suggesting either transdifferentiation or the persistence of a multipotent progenitor. Here, we show that clonable skeletal myogenic cells are present in the embryonic dorsal aorta of mouse embryos. This finding is based on a detailed clonal analysis of different tissue anlagen at various developmental stages. In vitro, these myogenic cells show the same morphology as satellite cells derived from adult skeletal muscle, and express a number of myogenic and endothelial markers. Surprisingly, the latter are also expressed by adult satellite cells. Furthermore, it is possible to clone myogenic cells from limbs of mutant c-Met−/− embryos, which lack appendicular muscles, but have a normal vascular system. Upon transplantation, aorta-derived myogenic cells participate in postnatal muscle growth and regeneration, and fuse with resident satellite cells.The potential of the vascular system to generate skeletal muscle cells may explain observations of nonsomite skeletal myogenesis and raises the possibility that a subset of satellite cells may derive from the vascular system.

Muscle stem cells and model systems for their investigation

“…These interstitial cells are similar to previously described mesoangioblasts (De Angelis et al, 1999;Minasi et al, 2002) residing in the embryonic dorsal aorta. However, unlike mesoangioblasts, they do not express endothelial markers, but instead express markers of pericytes such as alkaline phosphatase.…”

“…For all these reasons, the attention has turned to other sources of donor cells and in particular the embryonic vasculature-derived mesoangioblasts (De Angelis et al, 1999;Minasi et al, 2002;Galvez et al, 2006), their adult counterparts, the pericytes (Dellavalle et al, 2007), as well as the circulating AC133ϩ cells (Torrente et al, 2004) that appear to be the most promising candidates. The mesoangioblasts were found to repopulate and to repair diseased skeletal muscles in dystrophic mice and also in dystrophic golden retriever dogs, which represent a faithful model of human DMD .…”

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

“…43,54,55). Mice were sacrificed after 8 or 15 d. CD45 + CD11b + F4/80 + macrophages, as assessed by flow cytometry after enzymatic digestion of the tissue, effectively infiltrated the injured tissue whereas they were virtually absent in untreated muscle (Fig.…”

“…Other sources of myogenic precursors, mostly of mesodermic origin, have been identified (27)(28)(29)(30)(31)(32)(33)(34)(35)(36) including mesoangioblasts from the embryonic dorsal aorta and their counterparts associated with microvascular walls in the adult skeletal muscle, pericytes (37), and have been shown to contribute to muscle regeneration (36,(38)(39)(40)(41)(42). Upon transplantation in regenerating injured skeletal muscle, mesoangioblasts participate in tissue growth and regeneration and fuse with resident satellite cells (43). They have been used for therapy in dystrophic mice and dogs (44,45).…”

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

“…Although satellite cells are normally quiescent in adult muscle, they are responsible for muscle regeneration after injury and involved in work-or load-induced muscle fiber hypertrophy (Rosenblatt and Parry, 1992;Schultz and McCormick, 1994;De Angelis et al, 1999;Semsarian et al, 1999;Bodine et al, 2001).…”