iPSC-derived functional human neuromuscular junctions model the pathophysiology of neuromuscular diseases
iPSC-derived functional human neuromuscular junctions model the pathophysiology of neuromuscular diseases
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DOI：
10.1172/jci.insight.124299
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发表时间：
2019-09-19
期刊：
影响因子：
8
通讯作者：
Saito, Megumu K.
中科院分区：
文献类型：
--
作者：
Lin, Chuang-Yu;Yoshida, Michiko;Saito, Megumu K.
自主骨骼肌收缩的控制依赖于动作电位，动作电位通过神经肌肉接头（NMJ）从运动神经元发送信号。虽然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，我们提出了一个潜在的新的2步，自组织的方法，用于在体外产生人类NM的人诱导多能干细胞。我们简单而强大的方法导致了一个复杂的NMJ结构，包括功能连接，重演体内突触形成。我们使用这些体外NMJ来模拟脊髓性肌萎缩的病理特征，揭示NMJ形成和NMJ依赖性肌肉收缩的发育和功能缺陷。因此，我们的分化系统对于研究和理解人类NMJ的生理和病理是有用的。
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 NM's 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.