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The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal
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The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal
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Journal Article
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal
2018
Overview
Pw1/Peg3
is an imprinted gene expressed from the paternally inherited allele. Several imprinted genes, including
Pw1/Peg3
, have been shown to regulate overall body size and play a role in adult stem cells.
Pw1/Peg3
is expressed in muscle stem cells (satellite cells) as well as a progenitor subset of muscle interstitial cells (PICs) in adult skeletal muscle. We therefore examined the impact of loss-of-function of
Pw1/Peg3
during skeletal muscle growth and in muscle stem cell behavior. We found that constitutive loss of
Pw1/Peg3
function leads to a reduced muscle mass and myofiber number. In newborn mice, the reduction in fiber number is increased in homozygous mutants as compared to the deletion of only the paternal
Pw1/Peg3
allele, indicating that the maternal allele is developmentally functional. Constitutive and a satellite cell-specific deletion of
Pw1/Peg3
, revealed impaired muscle regeneration and a reduced capacity of satellite cells for self-renewal. RNA sequencing analyses revealed a deregulation of genes that control mitochondrial function. Consistent with these observations,
Pw1/Peg3
mutant satellite cells displayed increased mitochondrial activity coupled with accelerated proliferation and differentiation. Our data show that
Pw1/Peg3
regulates muscle fiber number determination during fetal development in a gene-dosage manner and regulates satellite cell metabolism in the adult.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/105
/ 13/31
/ 38
/ 38/23
/ 64
/ 64/60
/ Alleles
/ Animals
/ Cell Self Renewal - genetics
/ Fetal Development - genetics
/ Fetuses
/ Genes
/ Humanities and Social Sciences
/ Kruppel-Like Transcription Factors - physiology
/ Male
/ Mice
/ Muscle Development - genetics
/ Muscle Fibers, Skeletal - cytology
/ Muscle Fibers, Skeletal - physiology
/ RNA
/ Satellite Cells, Skeletal Muscle - metabolism
/ Science
