An adult tissue-specific stem cell in its niche: A gene profiling analysis of in vivo quiescent and activated muscle satellite cells
An adult tissue-specific stem cell in its niche: A gene profiling analysis of in vivo quiescent and activated muscle satellite cells
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DOI：
10.1016/j.scr.2009.10.003
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发表时间：
2010-03-01
影响因子：
1.2
通讯作者：
Buckingham, Margaret
中科院分区：
文献类型：
--
作者：
Pallafacchina, Giorgia;Francois, Stephanie;Buckingham, Margaret
骨骼肌的卫星细胞为静止和激活的组织干细胞状态提供了范例。我们已经对通过流式细胞术从Pax 3（GFP/+）小鼠纯化的卫星细胞进行了转录组分析。我们比较了来自成年骨骼肌的样本，其中卫星细胞主要是静止的，与来自生长中的肌肉或再生（mdx）肌肉的样本，其中它们被激活。对两种激活状态共享的调节的分析避免了由于不成熟或病理条件引起的其他影响。这种体内特征不同于先前分析的细胞培养后激活的卫星细胞。它揭示了卫星细胞如何保护自己免受损害并保持静止，同时在收到适当的信号时被激活。这是说明了辅阻遏物Dach 1的操作，并通过演示，静态卫星细胞更好地保护氧化应激比那些从mdx或1周龄的肌肉。静止与体内激活的比较也为卫星细胞如何通过细胞粘附和基质重塑控制其在肌纤维上的生态位提供了新的见解。后者还通过蛋白聚糖修饰增强生长因子活性。当蛋白酶的表达上调时，拆除细胞外基质对于卫星细胞活化是重要的，而其抑制剂的转录物在静止细胞中是高的。与此相一致，我们证明了金属蛋白酶的功能是体内有效再生所必需的。(C)2009爱思唯尔有限公司版权所有。
The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses on satellite cells purified by flow cytometry from Pax3(GFP/+) mice. We compared samples from adult skeletal muscles where satellite cells are mainly quiescent, with samples from growing muscles or regenerating (mdx) muscles, where they are activated. Analysis of regulation that is shared by both activated states avoids other effects due to immature or pathological conditions. This in vivo profile differs from that of previously analyzed satellite cells activated after cell culture. It reveals how the satellite cell protects itself from damage and maintains quiescence, while being primed for activation on receipt of the appropriate signal. This is illustrated by manipulation of the corepressor Dach1, and by the demonstration that quiescent satellite cells are better protected from oxidative stress than those from mdx or 1-week-old muscles. The quiescent versus in vivo activated comparison also gives new insights into how the satellite cell controls its niche on the muscle fiber through cell adhesion and matrix remodeling. The latter also potentiates growth factor activity through proteoglycan modification. Dismantling the extracellular matrix is important for satellite cell activation when the expression of proteinases is up-regulated, whereas transcripts for their inhibitors are high in quiescent cells. In keeping with this, we demonstrate that metalloproteinase function is required for efficient regeneration in vivo. (C) 2009 Elsevier B.V. All rights reserved.