The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal.
Correra, Rosa Maria
Ferguson-Smith, Anne C
Springer Science and Business Media LLC
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Correra, R. M., Ollitrault, D., Valente, M., Mazzola, A., Adalsteinsson, B. T., Ferguson-Smith, A. C., Marazzi, G., & et al. (2018). The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal.. Sci Rep, 8 (1), 14649. https://doi.org/10.1038/s41598-018-32941-x
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.
Cells, Cultured, Satellite Cells, Skeletal Muscle, Animals, Animals, Newborn, Mice, Transgenic, Mice, Models, Animal, Regeneration, Genomic Imprinting, Fetal Development, Muscle Development, Gene Dosage, Male, Kruppel-Like Transcription Factors, Muscle Fibers, Skeletal, Cell Self Renewal
Medical Research Council (MR/R009791/1)
External DOI: https://doi.org/10.1038/s41598-018-32941-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285694
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/