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Fig. 7. A proposed model for the mesenchymal plasticity of skeletal muscle satellite cells. As shown, satellite cells in an appropriate myogenic environment enter myogenic differentiation, yielding myoblasts that form myotubes. De-homed satellite cells enter the MAD route, yielding non-myogenic cells such as adipocytes and osteoblasts. Inappropriate cues within the muscle may direct satellite cells into the MAD program at the expense of myogenesis. Mesenchymal stem cells residing in the bone marrow are in a MAD-equivalent state and when de-homed can give rise to variety of cell types including satellite cells when reaching skeletal muscle. Note that although the diversion of satellite cells into the MAD program and its culmination with mature adipocytes is based on data provided in the present study, the diversion of satellite cells into osteogenesis via the MAD program is suggested based on studies reporting on the development of osteoblasts/chondroblasts in myogenic cultures treated with bone morphogenic proteins (e.g. Asakura et al., 2001; Katagiri et al., 1994). Likewise, the incorporation of bone marrow-derived cells into the myofiber unit as depicted in the model is based on published studies (Dreyfus et al., 2004; Gussoni et al., 1999; LaBarge and Blau, 2002). Such studies have not established that satellite cells are typically originated from bone marrow-derived cells but have shown that bone marrow-derived cells can infrequently enter the satellite cell niche and acquire myogenic properties.
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