Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Semin Cell Dev Biol. 2021 Nov;119:3-10. doi: 10.1016/j.semcdb.2021.04.015. Epub 2021 May 8.
Skeletal muscle cells are noteworthy for their syncytial nature, with each myofiber accumulating hundreds or thousands of nuclei derived from resident muscle stem cells (MuSCs). These nuclei are accrued through cell fusion, which is controlled by the two essential fusogens Myomaker and Myomerger that are transiently expressed within the myogenic lineage. While the absolute requirement of fusion for muscle development has been known for decades, the underlying need for the magnitude of multinucleation in muscle remains mysterious. Possible advantages of multinucleation include the potential it affords for transcriptional diversity within these massive cells, and as a means of increasing DNA content to support optimal cell size and function. In this article, we review recent advances that elucidate the relationship between myonuclear numbers and establishment of myofiber size, and discuss how this new information refines our understanding of the concept of myonuclear domains (MND), the cytoplasmic volumes that each resident myonucleus can support. Finally, we explore the potential consequences and costs of multinucleation and its impacts on myonuclear transcriptional reserve capacity, growth potential, myofiber size regulation, and muscle adaptability. We anticipate this report will not only serve to highlight the latest advances in the basic biology of syncytial muscle cells but also provide information to help design the next generation of therapeutic strategies to maintain muscle mass and function.
骨骼肌细胞因其合胞体性质而引人注目，每条肌纤维积累了数百或数千个源自肌卫星细胞（MuSCs）的核。这些核是通过细胞融合积累的，细胞融合由短暂表达于成肌谱系中的两个必需融合因子 Myomaker 和 Myomerger 控制。尽管几十年来人们已经知道融合对于肌肉发育的绝对必要性，但肌肉中多核化的巨大程度的潜在需求仍然是个谜。多核化的可能优势包括为这些巨大细胞内的转录多样性提供的潜力，以及作为增加 DNA 含量以支持最佳细胞大小和功能的一种手段。在本文中，我们回顾了最近的进展，这些进展阐明了肌核数量与肌纤维大小建立之间的关系，并讨论了这些新信息如何完善我们对肌核域（MND）概念的理解，即每个驻留肌核可以支持的细胞质体积。最后，我们探讨了多核化的潜在后果和代价，以及其对肌核转录储备能力、生长潜力、肌纤维大小调节和肌肉适应性的影响。我们预计，本报告不仅将突出合胞体骨骼肌细胞基础生物学的最新进展，还将提供信息，帮助设计下一代维持肌肉质量和功能的治疗策略。
