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Abnormal epigenetic...
Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects
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- Davegårdh, Cajsa (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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- Broholm, Christa (författare)
- Copenhagen University Hospital
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- 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
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- 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
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- Peijs, Lone (författare)
- University of Copenhagen
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- Hansen, Ninna Schiøler (författare)
- Copenhagen University Hospital
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- Volkov, Petr (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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- Kjøbsted, Rasmus (författare)
- University of Copenhagen
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- Wojtaszewski, Jørgen F P (författare)
- University of Copenhagen
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- Pedersen, Maria (författare)
- University of Copenhagen
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- Pedersen, Bente Klarlund (författare)
- University of Copenhagen
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- Ballak, Dov B. (författare)
- University of Colorado
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- Dinarello, Charles A. (författare)
- Radboud University Nijmegen,University of Colorado
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- Heinhuis, Bas (författare)
- Radboud University Nijmegen
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- Joosten, Leo A B (författare)
- Radboud University Medical Center
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- Nilsson, Emma (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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- Vaag, Allan (författare)
- AstraZeneca, Sweden,Copenhagen University Hospital
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- Scheele, Camilla (författare)
- University of Copenhagen
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- 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)
- 2017-02-22
- 2017
- Engelska 27 s.
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 1-27
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://bmcmedicine....
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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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)
Nyckelord
- ARPP21
- CGB
- DNA methylation
- Epigenetics
- IL-32
- Insulin resistance
- MT
- Myogenesis
- Obesity
- PSG
- TGF-β3
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Davegårdh, Cajsa
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Broholm, Christa
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Perfilyev, Alexa ...
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Henriksen, Tora
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García-Calzón, S ...
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Peijs, Lone
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visa fler...
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Hansen, Ninna Sc ...
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Volkov, Petr
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Kjøbsted, Rasmus
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Wojtaszewski, Jø ...
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Pedersen, Maria
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Pedersen, Bente ...
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Ballak, Dov B.
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Dinarello, Charl ...
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Heinhuis, Bas
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Joosten, Leo A B
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Nilsson, Emma
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Vaag, Allan
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Scheele, Camilla
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Ling, Charlotte
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MEDICIN OCH HÄLS ...
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BMC Medicine
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Lunds universitet