Highly coordinated gene regulation in mouse skeletal muscle regeneration.
Mammalian skeletal muscles are capable of regeneration after injury. Quiescent satellite cells are activated to reenter the cell cycle and to differentiate for repair, recapitulating features of myogenesis during embryonic development. To understand better the molecular mechanism involved in this process in vivo, we employed high density cDNA microarrays for gene expression profiling in mouse tibialis anterior muscles after a cardiotoxin injection. Among 16,267 gene elements surveyed, 3,532 elements showed at least a 2.5-fold change at one or more time points during a 14-day time course. Hierarchical cluster analysis and semiquantitative reverse transcription-PCR showed induction of genes important for cell cycle control and DNA replication during the early phase of muscle regeneration. Subsequently, genes for myogenic regulatory factors, a group of imprinted genes and genes with functions to inhibit cell cycle progression and promote myogenic differentiation, were induced when myogenic stem cells started to differentiate. Induction of a majority of these genes, including E2f1 and E2f2, was abolished in muscles lacking satellite cell activity after gamma radiation. Regeneration was severely compromised in E2f1 null mice but not affected in E2f2 null mice. This study identifies novel genes potentially important for muscle regeneration and reveals highly coordinated myogenic cell proliferation and differentiation programs in adult skeletal muscle regeneration in vivo.
Yan
Zhen
Z
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. zhen.yan@duke.edu
Choi
Sangdun
S
Liu
Xuebin
X
Zhang
Mei
M
Schageman
Jeoffrey J
JJ
Lee
Sun Young
SY
Hart
Rebecca
R
Lin
Ling
L
Thurmond
Frederick A
FA
Williams
R Sanders
RS
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D004179:Cobra Cardiotoxin Proteins / Q000008:administration & dosage; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018816:Genes, cdc; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004179:Cobra Cardiotoxin Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors