Study of muscle cell dedifferentiation after skeletal muscle injury of mice with a Cre-Lox system |
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Authors: | Mu Xiaodong Peng Hairong Pan Haiying Huard Johnny Li Yong |
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Affiliation: | The Laboratory of Molecular Pathology, Stem Cell Research Center (SCRC), Children's Hospital of UPMC, Pittsburgh, Pennsylvania, USA. |
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Abstract: | BackgroundDedifferentiation of muscle cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle cell dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated cell populations of myotubes and non-fused mononuclear cells, including stem cells that can coexist within the population of cells being studied.Methodology/Principal FindingsIn the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear cells can develop into a variety of different muscle cell lineages, i.e., myoblasts, satellite cells, and muscle derived stem cells.Conclusions/SignificanceThese novel findings demonstrated, for the first time, that cellular dedifferentiation of skeletal muscle cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo. |
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