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Sökning: WFRF:(Vaag Allan) > Scheele Camilla > Garcia Calzon Sonia > Abnormal epigenetic...

  • Davegårdh, CajsaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups (författare)

Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • 2017-02-22
  • Springer Science and Business Media LLC,2017
  • 27 s.

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:e21ebac6-9b4d-4470-83f5-9abf1704a593
  • https://lup.lub.lu.se/record/e21ebac6-9b4d-4470-83f5-9abf1704a593URI
  • https://doi.org/10.1186/s12916-017-0792-xDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Background: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. Methods: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. Results: We observed genome-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic mice had reduced insulin response and muscle weight. Remarkably, approximately 3.7 times more methylation changes (147,161 versus 39,572) were observed during differentiation of myoblasts from obese versus non-obese subjects. In accordance, DNMT1 expression increased during myogenesis only in obese subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. Conclusions: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic epigenome during differentiation of human muscle stem cells and reveals abnormal epigenetic changes in obesity.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Broholm, ChristaCopenhagen University Hospital (författare)
  • Perfilyev, AlexanderLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-apy (författare)
  • Henriksen, ToraUniversity of Copenhagen (författare)
  • García-Calzón, SoniaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-sg_ (författare)
  • Peijs, LoneUniversity of Copenhagen (författare)
  • Hansen, Ninna SchiølerCopenhagen University Hospital (författare)
  • Volkov, PetrLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-pvo (författare)
  • Kjøbsted, RasmusUniversity of Copenhagen (författare)
  • Wojtaszewski, Jørgen F PUniversity of Copenhagen (författare)
  • Pedersen, MariaUniversity of Copenhagen (författare)
  • Pedersen, Bente KlarlundUniversity of Copenhagen (författare)
  • Ballak, Dov B.University of Colorado (författare)
  • Dinarello, Charles A.Radboud University Nijmegen,University of Colorado (författare)
  • Heinhuis, BasRadboud University Nijmegen (författare)
  • Joosten, Leo A BRadboud University Medical Center (författare)
  • Nilsson, EmmaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)geol-eno (författare)
  • Vaag, AllanAstraZeneca, Sweden,Copenhagen University Hospital(Swepub:lu)med-ava (författare)
  • Scheele, CamillaUniversity of Copenhagen (författare)
  • Ling, CharlotteLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)endo-cl0 (författare)
  • -lup-obsoleteForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:BMC Medicine: Springer Science and Business Media LLC15:1, s. 1-271741-7015

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