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中文摘要
翻译
摘要 骨骼肌组织得到维护,并可通过以下方式动态建模以满足持续需求 肌肉活动的变化。肌纤维,构成肌肉收缩元件的初级细胞 骨骼肌是有丝分裂后的,由被称为卫星细胞的干细胞库维持, 定位于肌纤维和覆盖的基底板之间的缝隙。因此而导致的流动性丧失 骨骼肌功能的丧失是损伤后发生的,是衰老的必然结果 以及许多神经肌肉疾病的后果,后两种疾病导致生活质量下降 发病率增加,需要住院或家庭护理,显著提高了医疗保健水平 成本。这些复杂的生理变化是有据可查的,但导致 这些变化并不为人所知。 卫星细胞可以(I)更新自己的种群,(Ii)致力于成肌细胞谱系并促进- 作为成肌细胞存活,以及(Iii)经历末端分化并融合成现有的肌纤维或 融合形成新的肌纤维,如肌核。卫星细胞在成人肌肉中广泛更新,但与 卫星细胞的数量基本保持不变。在诱发卫星细胞损伤后 数量恢复到受伤前的数量,这表明对卫星细胞的控制非常严格 数字。这些观察促使人们问,卫星细胞的数量是如何保持的,是什么 是卫星细胞周转的功能吗? 诱导性肌肉损伤后的定时EDU给药显示干细胞的产生 只有在损伤后4-5d肌核扩张完成后方可进行体内实验。因此,快速扩张-- 在肌肉损伤时发生的成肌细胞的Sion专门用于经历终末的细胞 分化以产生肌核。是什么机制阻止了再生过程中的早期自我更新- 一旦产生了足够的肌核,然后促进自我更新?当SC最有可能出现时 通过非对称除法,我们在这一应用中提出的实验的一个主要目标是 进一步了解骨骼肌再生过程中干细胞自我更新的机制。 提顿。 我们认为,在肌肉恢复过程中,卫星细胞的恢复需要不对称分裂。 一代。来自异位激活的成纤维细胞生长因子受体1的信号同时抑制末端 分化,导致不对称,促进不对称分裂。我们计划通过以下方式来测试这一想法 初步表征肌肉再生过程中卫星细胞的自我更新,然后鉴定Ge-Ge。 卫星细胞自我更新所需的磁相互作用,然后识别遗传交互作用 需要卫星细胞自我更新。
英文摘要
Summary Skeletal muscle tissue is maintained and can be dynamically modeled to fit ongoing needs by changes in muscular activity. Myofibers, the primary cells that comprise the contractile elements of skeletal muscle, are post-mitotic and maintained by a pool of stem cells, termed satellite cells, which are localized to a niche between the myofiber and overlying basal lamina. Loss of mobility arising from loss of skeletal muscle function occurs following an injury, is an inevitable consequence of aging and a consequence of many neuromuscular diseases, the latter two resulting in reduced quality of life and increased morbidity, requiring hospitalization or home care, significantly raising health care costs. These complex physiological changes are well documented but the mechanisms responsible for these changes are not understood. Satellite cells can (i) renew their own population, (ii) commit to the myoblast lineage and pro- liferate as myoblasts, and (iii) undergo terminal differentiation and fuse into existing myofibers or fuse to form new myofibers as myonuclei. Satellite cell turnover is extensive in adult muscle yet rela- tively constant numbers of satellite cells are maintained. Following an induced injury satellite cell numbers return to their pre-injury numbers, suggesting remarkably stringent control of satellite cell numbers. These observations prompt one to ask how satellite cell numbers are maintained and what is the function of satellite cell turnover? Timed EdU administration following an induced muscle injury revealed that SCs are generated only upon completion of myonuclear expansion at ~4-5d post-injury in vivo. Thus, the rapid expan- sion of myoblasts occurring upon muscle injury is exclusively devoted to cells that undergo terminal differentiation to produce myonuclei. What mechanisms prevent self-renewal early during regenera- tion and then promote self-renewal once sufficient myonuclei are generated? As SCs most likely arise by asymmetric division, a major goal of our proposed experiments in this application are aimed to gain a better understand the mechanisms governing SC self-renewal during skeletal muscle regenera- tion. We propose that asymmetric division is required for satellite cell restoration during muscle re- generation. Signaling from ectopically activated FGF Receptor 1 simultaneously represses terminal differentiation, induces asymmetry and promotes asymmetric division. We plan to test this idea by initially characterizing satellite cell self-renewal during muscle regeneration, and then identifying ge- netic interactions required for satellite cell self-renewal and then to identify genetic interactions re- quired for satellite cell self-renewal.
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Replicative Potential of Muscle Stem Cells
  • 批准号:
    10685322
  • 项目类别:
  • 资助金额:
    $50.73万
  • 财政年份:
    2017
  • 负责人:
    Bradley B Olwin
  • 依托单位:
Replicative Potential of Muscle Stem Cells
  • 批准号:
    10530885
  • 项目类别:
  • 资助金额:
    $52.74万
  • 财政年份:
    2017
  • 负责人:
    Bradley B Olwin
  • 依托单位:
Replicative Potential of Muscle Stem Cells
  • 批准号:
    9403495
  • 项目类别:
  • 资助金额:
    $33.88万
  • 财政年份:
    2017
  • 负责人:
    Bradley B Olwin
  • 依托单位:
Age-Dependent Regulation of Muscle Stem Cell Homeostasis
  • 批准号:
    8688866
  • 项目类别:
  • 资助金额:
    $33.84万
  • 财政年份:
    2011
  • 负责人:
    Bradley B Olwin
  • 依托单位:
海外基金