The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal
Abstract 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...
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doaj-586cd7a187fa4bc7bf928acf227712842020-12-08T03:21:14ZengNature Publishing GroupScientific Reports2045-23222018-10-018111410.1038/s41598-018-32941-xThe imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewalRosa Maria Correra0David Ollitrault1Mariana Valente2Alessia Mazzola3Bjorn T. Adalsteinsson4Anne C. Ferguson-Smith5Giovanna Marazzi6David A. Sassoon7UMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIUMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIUMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIUMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIDepartment of Physiology Development and Neuroscience, Downing Street, University of CambridgeDepartment of Genetics, University of Cambridge, Downing StreetUMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIUMR S 1166 INSERM (Stem Cells and Regenerative Medicine Team), University of Pierre and Marie Curie Paris VIAbstract 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.https://doi.org/10.1038/s41598-018-32941-xSatellite CellsMyofiber NumberSkeletal Muscle Fiber NumberMaternal AlleleMutant Muscle |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosa Maria Correra David Ollitrault Mariana Valente Alessia Mazzola Bjorn T. Adalsteinsson Anne C. Ferguson-Smith Giovanna Marazzi David A. Sassoon |
spellingShingle |
Rosa Maria Correra David Ollitrault Mariana Valente Alessia Mazzola Bjorn T. Adalsteinsson Anne C. Ferguson-Smith Giovanna Marazzi David A. Sassoon The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal Scientific Reports Satellite Cells Myofiber Number Skeletal Muscle Fiber Number Maternal Allele Mutant Muscle |
author_facet |
Rosa Maria Correra David Ollitrault Mariana Valente Alessia Mazzola Bjorn T. Adalsteinsson Anne C. Ferguson-Smith Giovanna Marazzi David A. Sassoon |
author_sort |
Rosa Maria Correra |
title |
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
title_short |
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
title_full |
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
title_fullStr |
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
title_full_unstemmed |
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
title_sort |
imprinted gene pw1/peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-10-01 |
description |
Abstract 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. |
topic |
Satellite Cells Myofiber Number Skeletal Muscle Fiber Number Maternal Allele Mutant Muscle |
url |
https://doi.org/10.1038/s41598-018-32941-x |
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