Pallafacchina Giorgia, François Stéphanie, Regnault Béatrice, Czarny Bertrand, Dive Vincent, Cumano Ana, Montarras Didier, Buckingham Margaret
Molecular Genetics of Development Unit, Department of Developmental Biology, URA CNRS 2578, Institut Pasteur, Paris, France.
Stem Cell Res. 2010 Mar;4(2):77-91. doi: 10.1016/j.scr.2009.10.003. Epub 2009 Oct 28.
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.
骨骼肌卫星细胞为静止和激活状态的组织干细胞提供了一个范例。我们对通过流式细胞术从Pax3(GFP/+)小鼠中纯化得到的卫星细胞进行了转录组分析。我们将主要处于静止状态的成年骨骼肌中的样本，与生长中的肌肉或再生（mdx）肌肉中的样本进行了比较，在这些肌肉中卫星细胞处于激活状态。对两种激活状态共有的调控进行分析，避免了因不成熟或病理状况产生的其他影响。这种体内情况与之前分析的细胞培养后激活的卫星细胞不同。它揭示了卫星细胞如何在接收到适当信号时准备激活的同时，保护自身免受损伤并维持静止状态。这通过对共抑制因子Dach1的操作以及静止卫星细胞比mdx或1周龄肌肉中的卫星细胞更能抵御氧化应激的证明得以说明。静止与体内激活状态的比较还为卫星细胞如何通过细胞黏附和基质重塑来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。当蛋白酶表达上调时，拆解细胞外基质对卫星细胞激活很重要，而其抑制剂的转录本在静止细胞中含量很高。与此一致，我们证明金属蛋白酶功能是体内有效再生所必需的。
