Induced pluripotent stem cells (iPSCs) have revolutionized human biomedicine through their use in disease modeling and therapy. In comparison, little progress has been made toward the application of iPSCs in veterinary species. In that regard, skeletal myocytes from iPSCs would have great potential for understanding muscle function and disease in the equine athlete. In this study, we generated skeletal myotubes by transducing equine iPSC-derived mesenchymal derivatives with an inducible lentiviral vector coding for the human sequence of the myogenic factor, MyoD. Myosin heavy chain-positive myotubes generated from two different iPSC lines were compared to myotubes from adult equine skeletal muscle progenitor cells (MPCs). iPSC myotubes had a smaller mean area than MPC myotubes (≤2-fold). In addition, quantitative polymerase chain reaction analyses showed that iPSC myotubes expressed MYH2 and MYH3 isoforms (at similar or lower levels than MPC myotubes), but they did not express the mature muscle isoform, MYH1. Compared to MPC myotubes, iPSC myotubes expressed reduced levels of the myogenic factors, MYOD1 and MYF6, but did not express MYF5. Finally, iPSC myotubes responded to KCl-induced membrane depolarization by releasing calcium and did so in a manner similar to MPC myotubes. In conclusion, this is the first study to report the generation of functional myocytes from equine iPSCs.

中文翻译：

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从马诱导多能干细胞中产生功能性心肌细胞。

诱导多能干细胞（iPSC）通过在疾病模型和治疗中的应用，彻底改变了人类生物医学。相比之下，在将iPSC应用于兽医物种方面进展甚微。在这方面，来自iPSC的骨骼肌细胞将具有极大的潜力来了解马运动员的肌肉功能和疾病。在这项研究中，我们通过用可诱导的慢病毒载体转导马iPSC来源的间充质衍生物来生成骨骼肌管，该慢病毒载体编码肌源性因子MyoD的人类序列。将两种不同的iPSC系产生的肌球蛋白重链阳性肌管与成年马骨骼肌祖细胞（MPC）的肌管进行了比较。iPSC肌管的平均面积小于MPC肌管（≤2倍）。此外，定量聚合酶链反应分析表明，iPSC肌管表达MYH2和MYH3同工型（与MPC肌管相似或更低），但不表达成熟的肌肉同工型MYH1。与MPC肌管相比，iPSC肌管表达的肌原性因子MYOD1和MYF6降低，但不表达MYF5。最后，iPSC肌管通过释放钙对KCl诱导的膜去极化作出反应，并以类似于MPC肌管的方式进行。总之，这是第一个报告马iPSC产生功能性心肌细胞的研究。MYOD1和MYF6，但未表示MYF5。最后，iPSC肌管通过释放钙对KCl诱导的膜去极化作出反应，并以类似于MPC肌管的方式进行。总之，这是第一个报告马iPSC产生功能性心肌细胞的研究。MYOD1和MYF6，但未表示MYF5。最后，iPSC肌管通过释放钙对KCl诱导的膜去极化作出反应，并以类似于MPC肌管的方式进行。总之，这是第一个报告马iPSC产生功能性心肌细胞的研究。