An adult tissue-specific stem cell in its niche: A gene profiling analysis of in vivo quiescent and activated muscle satellite cells

摘要

The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We havecarried out transcriptome analyses on satellite cells purified by flow cytometry from Pax3~(GFP/+)mice. We compared samplesfrom 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 dueto immature or pathological conditions. This in vivo profile differs from that of previously analyzed satellite cells activatedafter cell culture. It reveals how the satellite cell protects itself from damage and maintains quiescence, while being primed foractivation on receipt of the appropriate signal. This is illustrated by manipulation of the corepressor Dach1, and by thedemonstration that quiescent satellite cells are better protected from oxidative stress than those from mdx or 1-week-oldmuscles. The quiescent versus in vivo activated comparison also gives new insights into how the satellite cell controls its nicheon the muscle fiber through cell adhesion and matrix remodeling. The latter also potentiates growth factor activity throughproteoglycan modification. Dismantling the extracellular matrix is important for satellite cell activation when the expression ofproteinases is up-regulated, whereas transcripts for their inhibitors are high in quiescent cells. In keeping with this, wedemonstrate that metalloproteinase function is required for efficient regeneration in vivo.