| Title |
Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects
|
|---|---|
| Published in |
BMC Medicine, February 2017
|
| DOI | 10.1186/s12916-017-0792-x |
| Pubmed ID | |
| Authors |
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F. P. Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B. Ballak, Charles A. Dinarello, Bas Heinhuis, Leo A. B. Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling |
| Abstract |
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. 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. 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. 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. |
X Demographics
The data shown below were collected from the profiles of 23 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 6 | 26% |
| United States | 4 | 17% |
| Switzerland | 1 | 4% |
| Spain | 1 | 4% |
| Norway | 1 | 4% |
| Canada | 1 | 4% |
| Netherlands | 1 | 4% |
| Bulgaria | 1 | 4% |
| Unknown | 7 | 30% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 16 | 70% |
| Scientists | 4 | 17% |
| Practitioners (doctors, other healthcare professionals) | 2 | 9% |
| Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
The data shown below were compiled from readership statistics for 117 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | <1% |
| Unknown | 116 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 17 | 15% |
| Researcher | 16 | 14% |
| Student > Master | 14 | 12% |
| Student > Bachelor | 11 | 9% |
| Student > Postgraduate | 9 | 8% |
| Other | 27 | 23% |
| Unknown | 23 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 31 | 26% |
| Medicine and Dentistry | 21 | 18% |
| Agricultural and Biological Sciences | 18 | 15% |
| Sports and Recreations | 7 | 6% |
| Nursing and Health Professions | 3 | 3% |
| Other | 9 | 8% |
| Unknown | 28 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 97. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 December 2017.
All research outputs
#384,804
of 23,577,761 outputs
Outputs from BMC Medicine
#299
of 3,569 outputs
Outputs of similar age
#8,922
of 312,460 outputs
Outputs of similar age from BMC Medicine
#9
of 68 outputs
Altmetric has tracked 23,577,761 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,569 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 44.5. This one has done particularly well, scoring higher than 91% of its peers.
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We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.