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

基本信息

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
项目类别：
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

项目摘要

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.

Twist2 肌源祖细胞在成人骨骼肌中的作用项目概要/摘要成人骨骼肌在生理和病理条件下能够适应肌肉质量和肌纤维大小机械超负荷和激素刺激会导致肌肉以肥大的形式生长。并增强肌肉力量和功能，相反，随着年龄的增长，肌肉质量和力量会减少。该疾病具有深远的负面影响，导致世界各地的人虚弱、残疾和死亡。老年人口急剧增长，迫切需要了解维持的需求最近，我们开发了肌肉减少症和恶病质的治疗方法。鉴定出一种新的肌源性祖细胞，其特征是 bHLH 转录因子 Twis2 (Tw2 In) 的表达。成人肌肉中，Tw2 在间质细胞中表达，但在成熟肌纤维或卫星细胞中不表达。追踪显示 Tw2+ 祖细胞群对成人 IIb/x 型肌纤维有特异性贡献这些 Tw2+ 细胞的消融会导致 IIb 型纤维特异性。这些发现强调了 Tw2+ 细胞在维持 IIb 型方面的独特作用。该项目的总体目标旨在破译衰老过程中的肌纤维。 Tw2+ 细胞有助于形成 IIb/x 型肌纤维，以阐明 Tw2 控制干性的机制和 Tw2+ 细胞的静止，并定义 Tw2+ 细胞在骨骼肌肥大和萎缩中的作用。最终，我们希望利用这些见解来开发新的策略来治疗性调节肌肉质量，衰老和疾病期间的力量和功能。