Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
JCI Insight. 2019 Sep 19;4(18):124299. doi: 10.1172/jci.insight.124299.
The control of voluntary skeletal muscle contraction relies on action potentials, which send signals from the motor neuron through the neuromuscular junction (NMJ). Although dysfunction of the NMJ causes various neuromuscular diseases, a reliable in vitro system for disease modeling is currently unavailable. Here, we present a potentially novel 2-step, self-organizing approach for generating in vitro human NMJs from human induced pluripotent stem cells. Our simple and robust approach results in a complex NMJ structure that includes functional connectivity, recapitulating in vivo synapse formation. We used these in vitro NMJs to model the pathological features of spinal muscular atrophy, revealing the developmental and functional defects of NMJ formation and NMJ-dependent muscular contraction. Our differentiation system is therefore useful for investigating and understanding the physiology and pathology of human NMJs.
自主骨骼肌收缩的控制依赖于动作电位，它将信号从运动神经元通过神经肌肉接头 (NMJ) 传递。尽管 NMJ 的功能障碍会导致各种神经肌肉疾病，但目前还没有可靠的体外疾病建模系统。在这里，我们提出了一种潜在的新两步、自组织方法，从人诱导多能干细胞中生成体外人 NMJ。我们的简单而强大的方法产生了一个复杂的 NMJ 结构，包括功能性连接，再现了体内突触形成。我们使用这些体外 NMJ 来模拟脊髓性肌萎缩症的病理特征，揭示了 NMJ 形成和 NMJ 依赖性肌肉收缩的发育和功能缺陷。因此，我们的分化系统可用于研究和理解人类 NMJ 的生理学和病理学。
