An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells.
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.
Pallafacchina
Giorgia
G
Molecular Genetics of Development Unit, Department of Developmental Biology, URA CNRS 2578, Institut Pasteur, Paris, France.
François
Stéphanie
S
Regnault
Béatrice
B
Czarny
Bertrand
B
Dive
Vincent
V
Cumano
Ana
A
Montarras
Didier
D
Buckingham
Margaret
M
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
C456264:Dach1 protein, mouse; D005136:Eye Proteins