Role of Twist2+ myogenic progenitor cells in adult skeletal muscle

Twist2 肌源祖细胞在成人骨骼肌中的作用

• 批准号: 9924250
• 负责人: Ning Liu
• 金额: $ 35.64万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924250
• 关键词: Ablation; Adult; Aging; Atrophic; Binding; Biological Assay; Cachexia; Cell fusion; Cell physiology; Cell surface; Cells; Disease; Elderly; Energy Metabolism; Fiber; Foundations; Genetic; Goals; Growth; Homeostasis; Hormones; Human body; Hypertrophy; In Vitro; Locomotion; Maintenance; Mechanics; Metabolism; Molecular; Molecular Profiling; Muscle; Muscle function; Muscular Atrophy; Myopathy; Natural regeneration; Pathologic; Physiological; Play; Population; Process; Role; Skeletal Muscle; Specificity; Testing; Therapeutic; Tissues; Tracer; Wild Type Mouse; Work; base; cell type; design; disability; experimental study; frailty; in vivo; insight; interstitial cell; mature animal; migration; mortality; muscle form; muscle hypertrophy; muscle regeneration; muscle strength; novel; novel therapeutic intervention; progenitor; receptor; sarcopenia; satellite cell; skeletal muscle wasting; stem cells; stemness; therapeutic development; transcription factor

Role of Twist2 myogenic progenitor cells in adult skeletal muscle Project Summary/Abstract Adult skeletal muscle can adapt muscle mass and myofiber size under physiological and pathological conditions. Mechanical overload and hormone stimulation result in muscle growth in the form of hypertrophy and enhanced muscle strength and function. In contrast, loss of muscle mass and strength during aging and disease has profound negative consequences, leading to frailty, disability and mortality. With the world’s elderly population growing dramatically, there is an urgent need to understand the requirements for maintaining muscle homeostasis and to development therapeutic treatments for sarcopenia and cachexia. Recently, we identified a novel myogenic progenitor marked by the expression of a bHLH transcription factor Twis2 (Tw2). In adult muscle, Tw2 is expressed in interstitial cells but not mature myofibers or satellite cells. Genetic lineage tracing revealed that the Tw2+ progenitor cell population contributes specifically to type IIb/x myofibers in adult muscle during homeostasis and regeneration. Ablation of these Tw2+ cells causes type IIb fiber specific myofiber atrophy during aging. These findings highlight the unique role of Tw2+ cells in maintaining type IIb myofibers during aging. The overall goals of this project are designed to decipher the mechanisms whereby Tw2+ cells contribute to type IIb/x myofibers, to elucidate the mechanisms whereby Tw2 controls stemness and quiescence of Tw2+ cells, and to define the roles of Tw2+ cells in skeletal muscle hypertrophy and atrophy. Ultimately, we hope to use these insights to develop new strategies to therapeutically modulate muscle mass, strength and function during aging and disease.

Twist 2肌源性祖细胞在成人骨骼肌中的作用 项目总结/摘要 成人骨骼肌在生理和病理条件下能适应肌肉质量和肌纤维大小的变化 条件机械超负荷和激素刺激导致肌肉以肥大的形式生长 增强肌肉力量和功能。相比之下，衰老过程中肌肉质量和力量的损失， 疾病具有严重的负面后果，导致虚弱、残疾和死亡。与世界 老年人口急剧增长，迫切需要了解维持 肌肉稳态和开发用于肌肉减少症和恶病质的治疗方法。最近我们 发现了一种新型肌源性祖细胞，其特征是表达bHLH转录因子Twis 2（Tw 2）。在 在成年肌肉中，Tw 2在间质细胞中表达，但不在成熟肌纤维或卫星细胞中表达。遗传谱系 追踪显示Tw 2+祖细胞群体特异性地贡献于成人中的IIb/x型肌纤维， 肌肉在体内平衡和再生过程中。这些Tw 2+细胞的消融导致IIb型纤维特异性 衰老过程中肌纤维萎缩这些发现强调了Tw 2+细胞在维持IIb型中的独特作用。 肌纤维老化该项目的总体目标旨在破译 Tw 2+细胞形成IIb/x型肌纤维，以阐明Tw 2控制干性的机制 Tw 2+细胞的表达和静止状态，明确Tw 2+细胞在骨骼肌肥大和萎缩中的作用。 最终，我们希望利用这些见解来开发新的策略来治疗调节肌肉质量， 在衰老和疾病期间的力量和功能。