Department of Stem Cell and Regenerative Biology, USA.
Dev Biol. 2012 Aug 15;368(2):323-34. doi: 10.1016/j.ydbio.2012.05.037. Epub 2012 Jun 15.
Mutations in the Survival of Motor Neuron (SMN) gene underlie the development of spinal muscular atrophy (SMA), which currently represents the leading genetic cause of mortality in infants and toddlers. SMA is characterized by degeneration of spinal cord motor neurons and muscle atrophy. Although SMA is often considered to be a motor neuron disease, accumulating evidence suggests that muscle cells themselves may be affected by low levels of SMN. Here, we examine satellite cells, tissue-resident stem cells that play an essential role in the growth and repair of skeletal muscle, isolated from a severe SMA mouse model (Smn(-/-); SMN2(+/+)). We found similar numbers of satellite cells in the muscles of SMA and wild-type (Smn(+/+); SMN2(+/+)) mice at postnatal day 2 (P2), and, when isolated from skeletal muscle using cell surface marker expression, these cells showed comparable survival and proliferative potential. However, SMA satellite cells differentiate abnormally, revealed by the premature expression of muscle differentiation markers, and, especially, by a reduced efficiency in forming myotubes. These phenotypes suggest a critical role of SMN protein in the intrinsic regulation of muscle differentiation and suggest that abnormal muscle development contributes to the manifestation of SMA symptoms.
运动神经元生存（SMN）基因突变是脊髓性肌萎缩症（SMA）发展的基础，目前该病是婴儿和幼儿死亡的主要遗传原因。SMA 的特征是脊髓运动神经元退化和肌肉萎缩。尽管 SMA 通常被认为是一种运动神经元疾病，但越来越多的证据表明，肌肉细胞本身可能受到低水平 SMN 的影响。在这里，我们研究了卫星细胞，即组织驻留的干细胞，它们在骨骼肌的生长和修复中发挥着重要作用，这些细胞是从严重的 SMA 小鼠模型（Smn(-/-); SMN2(+/+))中分离出来的。我们发现在出生后第 2 天（P2），SMA 和野生型（Smn(+/+); SMN2(+/+))小鼠的肌肉中卫星细胞数量相似，并且当使用细胞表面标志物表达从骨骼肌中分离出来时，这些细胞显示出相似的存活和增殖潜力。然而，SMA 卫星细胞的分化异常，表现为肌肉分化标志物的过早表达，特别是形成肌管的效率降低。这些表型表明 SMN 蛋白在肌肉分化的内在调节中起着关键作用，并表明异常的肌肉发育导致 SMA 症状的表现。
