Study of Muscle Cell Dedifferentiation after Skeletal Muscle Injury of Mice with a Cre-Lox System
Study of Muscle Cell Dedifferentiation after Skeletal Muscle Injury of Mice with a Cre-Lox System
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DOI：
10.1371/journal.pone.0016699
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发表时间：
2011-02-03
期刊：
影响因子：
3.7
通讯作者：
Li, Yong
中科院分区：
文献类型：
--
作者：
Mu, Xiaodong;Peng, Hairong;Li, Yong
背景：哺乳动物组织中肌肉细胞的去分化尚未观察到。骨骼肌细胞去分化研究面临的挑战之一是有一个可靠的模型，可以秘密地区分肌管和非融合单个核细胞的分化细胞群，包括可以在被研究细胞群中共存的干细胞。方法/主要发现：在当前的研究中，我们创建了一个Cre/Lox-β-半乳糖苷酶系统，它可以基于标记基因β-半乳糖苷酶的激活来特异性地标记分化的多核肌管和肌管生成的单核细胞。通过在成年小鼠模型中使用该系统，我们发现在肌肉损伤时，β-半乳糖苷酶阳性的多核肌纤维产生了β-半乳糖苷酶阳性的单核细胞。我们还证实了这些单个核细胞可以发育成多种不同的肌肉细胞谱系，即成肌细胞、卫星细胞和肌源性干细胞。结论/意义：这些新的发现首次证明，在活体内，哺乳动物骨骼肌创伤后确实发生了骨骼肌细胞的去分化。
Background: Dedifferentiation 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 Findings: In the current study, we created a Cre/Lox-beta-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear cells based on the activation of the marker gene, beta-galactosidase. By using this system in an adult mouse model, we found that beta-galactosidase positive mononuclear cells were generated from beta-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/Significance: These 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.