A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of survival of motor neuron protein.
A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of survival of motor neuron protein.
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DOI：
10.1016/j.ydbio.2012.05.037
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发表时间：
2012-08-15
影响因子：
2.7
通讯作者：
Rubin LL
中科院分区：
文献类型：
--
作者：
Hayhurst M;Wagner AK;Cerletti M;Wagers AJ;Rubin LL
运动神经元存活(SMN)基因突变是脊髓性肌萎缩症(SMA)发生的基础，目前SMA是婴幼儿死亡的主要遗传原因。SMA的特点是脊髓运动神经元变性和肌肉萎缩。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，即在骨骼肌生长和修复中发挥关键作用的组织驻留干细胞，从严重的SmA小鼠模型(Smn−/−；Smn2+/+)中分离出来。在出生后第2天(P2)，我们在SMA和野生型(SMN+/+；SMN+/+)小鼠的肌肉中发现了相似数量的卫星细胞，当使用细胞表面标记表达从骨骼肌分离时，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，并表明肌肉发育异常有助于SMA症状的表现。
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.
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影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
3.5
作者：
McGovern, Vicki L.;Gavrilina, Tatiana O.;Burghes, Arthur H. M.
通讯作者：
Burghes, Arthur H. M.
影响因子：
9.8
作者：
Campbell, L;Potter, A;Davies, K
通讯作者：
Davies, K
影响因子：
2.7
作者：
Lee YI;Mikesh M;Smith I;Rimer M;Thompson W
通讯作者：
Thompson W
影响因子：
3.5
作者：
Coovert, DD;Le, TT;Burghes, AHM
通讯作者：
Burghes, AHM