Slow-dividing satellite cells retain long-term self-renewal ability in adult muscle
Slow-dividing satellite cells retain long-term self-renewal ability in adult muscle
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DOI：
10.1242/jcs.096198
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发表时间：
2012-03-01
影响因子：
4
通讯作者：
Takeda, Shin'ichi
中科院分区：
文献类型：
--
作者：
Ono, Yusuke;Masuda, Satoru;Takeda, Shin'ichi
卫星细胞是肌肉干细胞，在出生后肌肉生长和成人肌肉再生中具有重要作用。虽然在活化的卫星细胞中观察到快速和缓慢分裂的群体，但它们之间的功能差异仍不清楚。在这里，我们阐明了增殖行为和卫星细胞功能之间的关系。为了评估细胞分裂的频率，用荧光染料PKH 26标记从小鼠EDL肌肉分离的卫星细胞，刺激增殖，然后通过FACS分选。绝大多数活化的卫星细胞是PKH26（低）快速分裂细胞，而PKH26（高）缓慢分裂细胞被观察到作为少数群体。快速分裂的细胞比缓慢分裂的细胞产生更多的分化和自我更新的细胞。然而，细胞来源于缓慢分裂的人口形成二次成肌细胞集落传代时，而那些从快速分裂的人口迅速经历成肌分化，而不产生自我更新的细胞后，几轮的细胞分裂。此外，缓慢分裂的细胞移植到损伤的肌肉中广泛地促进了体内肌肉再生。Id1是一种HLH蛋白，在所有活化的卫星细胞中都有表达，但在缓慢分裂的细胞群中表达水平不同。我们发现，保持长期自我更新能力的缓慢分裂细胞仅限于表达高水平Id1蛋白的未分化群体（PKH26（高）Id1（高）群体）。最后，全基因组基因表达分析描述了PKH26（高）Id1（高）群体的分子特征。总之，我们的研究结果表明，未分化的缓慢分裂的卫星细胞保留干细胞产生后代能够长期自我更新，因此可能是必不可少的肌肉稳态在整个生命。
Satellite cells are muscle stem cells that have important roles in postnatal muscle growth and adult muscle regeneration. Although fast-and slow-dividing populations in activated satellite cells have been observed, the functional differences between them remain unclear. Here we elucidated the relationship between proliferation behaviour and satellite cell function. To assess the frequency of cell division, satellite cells isolated from mouse EDL muscle were labelled with the fluorescent dye PKH26, stimulated to proliferate and then sorted by FACS. The vast majority of activated satellite cells were PKH26(low) fast-dividing cells, whereas PKH26(high) slow-dividing cells were observed as a minority population. The fast-dividing cells generated a higher number of differentiated and self-renewed cells compared with the slow-dividing cells. However, cells derived from the slow-dividing population formed secondary myogenic colonies when passaged, whereas those from the fast-dividing population rapidly underwent myogenic differentiation without producing self-renewing cells after a few rounds of cell division. Furthermore, slow-dividing cells transplanted into injured muscle extensively contributed to muscle regeneration in vivo. Id1, a HLH protein, was expressed by all activated satellite cells, but the expression level varied within the slow-dividing cell population. We show that the slow-dividing cells retaining long-term self-renewal ability are restricted to an undifferentiated population that express high levels of Id1 protein (PKH26(high) Id1(high) population). Finally, genome-wide gene expression analysis described the molecular characteristics of the PKH26(high) Id1(high) population. Taken together, our results indicate that undifferentiated slow-dividing satellite cells retain stemness for generating progeny capable of long-term self-renewal, and so might be essential for muscle homeostasis throughout life.