Neuroimmunology and Neuromuscular Disorders Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
J Neuropathol Exp Neurol. 2011 Feb;70(2):133-42. doi: 10.1097/NEN.0b013e3182084391.
Satellite cells are resident stem cells of adult skeletal muscle that have roles in tissue repair. Although several efforts have led to the functional characterization of distinct myogenic populations in animal models, the translation of these findings to humans has been limited. Here, we analyzed the expression and function of the neurotrophin receptor p75NTR in human skeletal muscle precursor cells. We combined histological investigations of muscle biopsies with molecular and cellular analyses of primary muscle precursor cells. p75NTR is expressed by most satellite cells in vivo and is a marker for regenerating fibers in inflamed and dystrophic muscle. p75NTR mRNA and protein are also detectable in primary myoblasts, and these levels increase transiently when cell differentiation is triggered. Transcriptome analyses of p75NTR high versus p75NTR low muscle cells showed that p75NTR is the prototype marker for a precursor cell population that has a broad transcriptional repertoire associated with muscle development and maturation. Several in vitro experiments, including receptor blockade and gene silencing in myoblasts, proved that p75NTR specifically regulates myogenesis and dystrophin expression. Taken together, the results indicate that p75NTR is a novel marker of human differentiation-prone muscle precursor cells that is involved in myogenesis in vivo and in vitro.
卫星细胞是成年骨骼肌中的常驻干细胞，在组织修复中发挥作用。尽管有几项研究努力导致了动物模型中不同成肌群体的功能特征得以阐明，但这些发现的转化在人类中受到限制。在这里，我们分析了神经营养因子受体 p75NTR 在人类骨骼肌前体细胞中的表达和功能。我们将肌肉活检的组织学研究与原代肌肉前体细胞的分子和细胞分析相结合。p75NTR 在体内由大多数卫星细胞表达，是炎症和萎缩肌肉中再生纤维的标志物。p75NTR mRNA 和蛋白也可在原代成肌细胞中检测到，当细胞分化被触发时，这些水平会短暂增加。p75NTR 高与 p75NTR 低的肌细胞的转录组分析表明，p75NTR 是一个前体细胞群体的原型标志物，该群体具有与肌肉发育和成熟相关的广泛转录谱。几项体外实验，包括成肌细胞中的受体阻断和基因沉默，证明了 p75NTR 特异性调节成肌作用和肌营养不良蛋白的表达。总之，这些结果表明 p75NTR 是一种新的人类分化倾向的肌肉前体细胞标志物，它参与体内和体外的成肌作用。
