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Sökning: onr:"swepub:oai:lup.lub.lu.se:e21ebac6-9b4d-4470-83f5-9abf1704a593" > Abnormal epigenetic...

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

Davegårdh, Cajsa (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
Broholm, Christa (författare)
Copenhagen University Hospital
Perfilyev, Alexander (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
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Henriksen, Tora (författare)
University of Copenhagen
García-Calzón, Sonia (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
Peijs, Lone (författare)
University of Copenhagen
Hansen, Ninna Schiøler (författare)
Copenhagen University Hospital
Volkov, Petr (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
Kjøbsted, Rasmus (författare)
University of Copenhagen
Wojtaszewski, Jørgen F P (författare)
University of Copenhagen
Pedersen, Maria (författare)
University of Copenhagen
Pedersen, Bente Klarlund (författare)
University of Copenhagen
Ballak, Dov B. (författare)
University of Colorado
Dinarello, Charles A. (författare)
University of Colorado,Radboud University Nijmegen
Heinhuis, Bas (författare)
Radboud University Nijmegen
Joosten, Leo A B (författare)
Radboud University Medical Center
Nilsson, Emma (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
Vaag, Allan (författare)
Copenhagen University Hospital,AstraZeneca, Sweden
Scheele, Camilla (författare)
University of Copenhagen
Ling, Charlotte (författare)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups
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 (creator_code:org_t)
BioMed Central (BMC), 2017
2017
Engelska 27 s.
Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 15:1, s. 1-27
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

ARPP21
CGB
DNA methylation
Epigenetics
IL-32
Insulin resistance
MT
Myogenesis
Obesity
PSG
TGF-β3

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