A population of myogenic stem cells that survives skeletal muscle aging
A population of myogenic stem cells that survives skeletal muscle aging
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DOI：
10.1634/stemcells.2006-0372
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Partridge, Terence A.
中科院分区：
文献类型：
--
作者：
Collins, Charlotte A.;Zammit, Peter S.;Partridge, Terence A.
分化的成体组织的完整性和功能的与胚胎干细胞相关的下降被广泛归因于驻留干细胞的数量或再生潜力的减少。卫星细胞位于骨骼肌肌纤维的基底膜下，是主要的肌源性干细胞。在这里，我们探讨了卫星细胞在老年小鼠肌肉再生骨骼肌和自我更新的能力，在组织培养和体内使用分离的肌纤维。卫星细胞表达Pax7从老年肌肉耗尽，当老年肌纤维被放置在文化中，卫星细胞肌源性进展导致细胞凋亡和更少的总分化后代。然而，少数培养的老年卫星细胞产生大集群的后代含有分化的细胞和新的细胞的静止的卫星细胞样表型特征的自我更新。平行的体内移植试验表明，尽管Pax7（+）细胞减少，但与单个老年肌纤维相关的卫星细胞群可以像与年轻肌纤维相关的较大卫星细胞群一样有效地再生肌肉和自我更新。我们的结论是，少数卫星细胞负责成人肌肉再生，这些干细胞在衰老的影响下存活下来，并在整个生命中保留其内在潜力。因此，干细胞介导的肌肉再生的有效性由外在环境影响和干细胞自身内在潜力的多样性决定。
Age-related decline in integrity and function of differentiated adult tissues is widely attributed to reduction in number or regenerative potential of resident stem cells. The satellite cell, resident beneath the basal lamina of skeletal muscle myofibers, is the principal myogenic stem cell. Here we have explored the capacity of satellite cells within aged mouse muscle to regenerate skeletal muscle and to self-renew using isolated myofibers in tissue culture and in vivo. Satellite cells expressing Pax7 were depleted from aged muscles, and when aged myofibers were placed in culture, satellite cell myogenic progression resulted in apoptosis and fewer total differentiated progeny. However, a minority of cultured aged satellite cells generated large clusters of progeny containing both differentiated cells and new cells of a quiescent satellite-cell-like phenotype characteristic of self-renewal. Parallel in vivo engraftment assays showed that, despite the reduction in Pax7(+) cells, the satellite cell population associated with individual aged myofibers could regenerate muscle and self-renew as effectively as the larger population of satellite cells associated with young myofibers. We conclude that a minority of satellite cells is responsible for adult muscle regeneration, and that these stem cells survive the effects of aging to retain their intrinsic potential throughout life. Thus, the effectiveness of stem-cell-mediated muscle regeneration is determined by both extrinsic environmental influences and diversity in intrinsic potential of the stem cells themselves.