Myofibres serve as the functional unit for locomotion, with the sarcomere as fundamental subunit. Running the entire length of this structure are hundreds of myonuclei, located at the periphery of the myofibre, juxtaposed to the plasma membrane. Myonuclear specialisation and clustering at the centre and ends of the fibre are known to be essential for muscle contraction, yet the molecular basis of this regionalisation has remained unclear. While the ‘myonuclear domain hypothesis’ helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on the diverse transcriptional programs running simultaneously within the syncytia and added a new perspective on how myonuclei communicate. Building upon this, we explore the critical cellular and molecular sources of transcriptional and functional heterogeneity within myofibres, discussing the impact of intrinsic and extrinsic factors on myonuclear programs. This knowledge provides new insights for understanding muscle development, repair, and disease, but also opens avenues for the development of novel and precise therapeutic approaches.

中文翻译：

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肌核的功能特化和协调

肌纤维作为运动的功能单位，肌节作为基本亚单位。数百个肌核贯穿该结构的整个长度，位于肌纤维的外围，与质膜并列。已知肌核的特化和纤维中心和末端的聚集对于肌肉收缩至关重要，但这种区域化的分子基础仍不清楚。虽然“肌核域假说”有助于解释肌核如何独立管理大的细胞质区域，但新技术为合胞体内同时运行的多种转录程序提供了粒度，并为肌核如何沟通提供了新的视角。在此基础上，我们探索了肌纤维内转录和功能异质性的关键细胞和分子来源，讨论了内在和外在因素对肌核程序的影响。这些知识为理解肌肉发育、修复和疾病提供了新的见解，同时也为开发新颖且精确的治疗方法开辟了途径。