Role of Twist2+ myogenic progenitor cells in adult skeletal muscle

Twist2成肌祖细胞在成人骨骼肌中的作用 项目摘要/摘要 成年骨骼肌在生理和病理条件下对肌肉质量和肌纤维大小的适应 条件。机械过载和激素刺激导致肌肉以肥大的形式生长 并增强肌肉力量和功能。相比之下，肌肉质量和力量的丧失在衰老和 疾病具有深刻的负面后果，导致虚弱、残疾和死亡。与世界上的 老年人口急剧增长，迫切需要了解维护的要求 肌肉动态平衡和开发治疗骨质疏松症和恶病质的方法。最近，我们 鉴定了一种新的肌源性前体细胞，其标志是bHLH转录因子Twi2(TW2)的表达。在……里面 在成年肌肉中，TW2表达于间质细胞，而不表达成熟的肌纤维或卫星细胞。遗传谱系 追踪显示，TW2+祖细胞群体对成人IIb/x型肌纤维具有特异性贡献 肌肉处于动态平衡和再生过程中。这些TW2+细胞的消融导致IIb型纤维特异性 肌纤维在老化过程中萎缩。这些发现突显了TW2+细胞在维持IIb型中的独特作用 老化过程中的肌纤维。该项目的总体目标旨在破译 TW2+细胞有助于IIb/x型肌纤维，以阐明TW2控制茎的机制 研究TW2+细胞在骨骼肌肥大和萎缩中的作用。 最终，我们希望利用这些洞察力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。

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.