Tsuji Ryosuke, Hayashi Takuto, Takahashi Satoru, Asakura Atsushi, Fujita Ryo
Laboratory Animal Resource Center in Transborder Medical Research Center, Department of Anatomy and Embryology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Muscle Stem Cells-Niche Interactions Team, Growth and Signaling Department, CNRS, INSERM, Institut Necker-Enfants Malades, Université Paris Cité, Paris, France.
Am J Physiol Cell Physiol. 2025 Jul 1;329(1):C200-C212. doi: 10.1152/ajpcell.00334.2025. Epub 2025 Jun 5.
Myogenic regulatory factors, including myoblast determination protein 1 (MyoD1 or MyoD) and myogenic factor 5 (Myf5), crucially regulate skeletal muscle lineage specification and development. Although MyoD and Myf5 exhibit overlapping functions during embryogenesis, their roles significantly diverge in adult muscles. Single knockout analysis revealed that MyoD uniquely regulates adult muscle regeneration, considerably influencing delayed myogenic differentiation, enhancing self-renewal, and modulating apoptosis resistance. These findings highlight fundamental differences between embryonic and adult myogenesis. Recent advances in single-cell technologies have revealed the heterogeneity of MyoD expression among adult muscle stem cells (MuSCs), thereby elucidating its diverse functional roles during muscle regeneration. Furthermore, MyoD has been implicated in the regulation of myofiber type specification and plasticity in mature skeletal muscles. Overall, these findings suggest that MyoD serves as a key orchestrator in cellular, functional, and pathological processes in adult skeletal muscle across multiple contexts. Although previous reviews have extensively addressed the role of MyoD in embryonic muscle development, the available literature lacks a focused discussion on its multifaceted functions in adult MuSCs, mature myofibers, and the aging process. In this review, we aimed to bridge this gap by integrating recent discoveries and offering novel insights into the dynamic roles of MyoD in adult skeletal muscles; the information discussed in this review has potential therapeutic implications in muscle regeneration, disease management, and combating age-related muscle decline.
生肌调节因子，包括成肌细胞决定蛋白1（MyoD1或MyoD）和成肌因子5（Myf5），对骨骼肌谱系的特化和发育起着至关重要的调节作用。虽然MyoD和Myf5在胚胎发育过程中表现出重叠的功能，但它们在成体肌肉中的作用却有显著差异。单基因敲除分析表明，MyoD独特地调节成体肌肉再生，对延迟的肌源性分化有显著影响，增强自我更新能力，并调节抗凋亡能力。这些发现突出了胚胎和成体肌生成之间的根本差异。单细胞技术的最新进展揭示了成体肌肉干细胞（MuSCs）中MyoD表达的异质性，从而阐明了其在肌肉再生过程中的多种功能作用。此外，MyoD还参与了成熟骨骼肌中肌纤维类型特化和可塑性的调节。总体而言，这些发现表明，MyoD在多种情况下是成体骨骼肌细胞、功能和病理过程中的关键协调者。尽管之前的综述广泛探讨了MyoD在胚胎肌肉发育中的作用，但现有文献缺乏对其在成体MuSCs、成熟肌纤维和衰老过程中多方面功能的集中讨论。在本综述中，我们旨在通过整合最近的发现，为MyoD在成体骨骼肌中的动态作用提供新的见解，弥合这一差距；本综述中讨论的信息在肌肉再生、疾病管理和对抗与年龄相关的肌肉衰退方面具有潜在的治疗意义。
