Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing significant deficits in muscle regeneration following injury. These results underscore the importance of neuromuscular junction and neural network as an essential niche of MuSCs. Determining the significance of MuSC-nerve interactions and their functional outcomes, as well as the possibility of modulating these connections, have important implications for our understanding of neuromuscular disease pathology and development of therapeutic interventions.

中文翻译：

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通过增强蛋白质合成和线粒体生物能，再生运动神经元启动肌肉干细胞的肌发生。

在整个生命中，骨骼肌是自愿运动的仲裁者，由一群称为骨骼肌卫星细胞（MuSC）的骨骼肌专用干细胞​​维持。与其他成年干细胞相似，MuSC的功能由其微环境或适当位置的细胞和无细胞成分紧密协调。虽然已经很好地描述了控制神经传递与肌肉收缩耦合的过程，但对于肌肉微环境中神经细胞与MuSC之间的相互串扰知之甚少。在这里，我们报告说，通过协同增强MuSC线粒体生物能和上调合成代谢蛋白的合成途径，轻度周围神经损伤可增强MuSC的肌源性功能和肌肉再生。我们还证明，神经肌肉突触的慢性破坏或退化，例如在肌肉营养不良和生物衰老中，将取消MuSC和运动神经元的相互作用，从而导致损伤后肌肉再生的明显缺陷。这些结果强调了神经肌肉接头和神经网络作为MuSCs必不可少的利基市场的重要性。确定MuSC-神经相互作用及其功能结果的重要性，以及调节这些联系的可能性，对我们对神经肌肉疾病病理学和治疗性干预措施的理解具有重要意义。这些结果强调了神经肌肉接头和神经网络作为MuSCs必不可少的利基市场的重要性。确定MuSC-神经相互作用及其功能结果的重要性，以及调节这些联系的可能性，对我们对神经肌肉疾病病理学和治疗性干预措施的理解具有重要意义。这些结果强调了神经肌肉接头和神经网络作为MuSCs必不可少的利基市场的重要性。确定MuSC-神经相互作用及其功能结果的重要性，以及调节这些联系的可能性，对我们对神经肌肉疾病病理学和治疗性干预措施的理解具有重要意义。