Skeletal Muscle Differentiation of Embryonic Mesoangioblasts Requires Pax3 Activity
Skeletal Muscle Differentiation of Embryonic Mesoangioblasts Requires Pax3 Activity
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DOI：
10.1634/stemcells.2008-0503
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Cossu, Giulio
中科院分区：
文献类型：
--
作者：
Messina, Graziella;Sirabella, Dario;Cossu, Giulio
中成血管细胞被描述为一群血管相关干细胞，能够分化成多种中胚层细胞类型，包括骨骼肌。在这里，我们报道配对盒转录因子 Pax3 在体外和体内指导小鼠中成血管细胞进行骨骼肌生成方面发挥着至关重要的作用。从 Pax3 缺失胚胎的主动脉中分离出的中成血管细胞的骨骼肌分化严重受损，而大多数其他分化程序不受 Pax3 缺失的影响。此外，Pax3(-/-)无效的中成血管细胞未能挽救α-肌聚糖突变小鼠的肌病表型。相比之下，来自Pax3功能获得的中成血管细胞Pax3(PAX3-FKHR/+)在体外表现出增强的肌生成，并且在这种肌营养不良模型中更有效地再生新的肌纤维。这些数据表明 Pax3 是中成血管细胞干细胞分化为骨骼肌所必需的，这与其在编排进入生肌程序中的作用保持一致。干细胞2009； 27：157-164
Mesoangioblasts have been characterized as a population of vessel-associated stem cells able to differentiate into several mesodermal cell types, including skeletal muscle. Here, we report that the paired box transcription factor Pax3 plays a crucial role in directing mouse mesoangioblasts toward skeletal myogenesis in vitro and in vivo. Mesoangioblasts isolated from the aorta of Pax3 null embryos are severely impaired in skeletal muscle differentiation, whereas most other differentiation programs are not affected by the absence of Pax3. Moreover, Pax3(-/-) null mesoangioblasts failed to rescue the myopathic phenotype of the alpha-sarcoglycan mutant mouse. In contrast, mesoangioblasts from Pax3 gain of function, Pax3(PAX3-FKHR/+), mice display enhanced myogenesis in vitro and are more efficient in regenerating new muscle fibers in this model of muscular dystrophy. These data demonstrate that Pax3 is required for the differentiation of mesoangioblast stem cells into skeletal muscle, in keeping with its role in orchestrating entry into the myogenic program. STEM CELLS 2009; 27: 157-164