PDF(Pubmed)
Abstract：
Human-induced pluripotent stem cells (hiPSCs) are a promising tool for disease modeling and drug screening. To apply them to skeletal muscle disorders, it is necessary to establish mature myotubes because the onset of many skeletal muscle disorders is after birth. However, to make mature myotubes, the forced expression of specific genes should be avoided, as otherwise dysregulation of the intracellular networks may occur. Here, we achieved this goal by purifying hiPSC-derived muscle stem cells (iMuSC) by Pax7-fluorescence monitoring and antibody sorting. The resulting myotubes displayed spontaneous self-contraction, aligned sarcomeres, and a triad structure. Notably, the phenotype of sodium channels was changed to the mature type in the course of the differentiation, and a characteristic current pattern was observed. Moreover, the protocol resulted in highly efficient differentiation and high homogeneity and is applicable to drug screening.
摘要：
人诱导多能干细胞(hiPSCs)是用于疾病建模和药物筛选的有希望的工具。将它们应用于骨骼肌疾病，有必要建立成熟的肌管，因为许多骨骼肌疾病的发作是在出生后。然而,制造成熟的肌管，应避免特定基因的强制表达，否则可能会发生细胞内网络的失调。这里,我们通过Pax7荧光监测和抗体分选纯化hiPSC衍生的肌肉干细胞（iMuSC）实现了这一目标。由此产生的肌管表现出自发的自我收缩，对齐的肉瘤，和三合会结构。值得注意的是,在分化过程中钠通道的表型变为成熟型,并观察到特征电流模式。此外，该方案产生了高效的分化和高度的同质性，适用于药物筛选。
