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Epigenome- and Tran...
Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men
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- Broholm, Christa (author)
- Copenhagen University Hospital
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- Ribel-Madsen, Rasmus (author)
- Danish Diabetes Academy,Copenhagen University Hospital
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- Hjort, Line (author)
- University of Copenhagen,Copenhagen University Hospital
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- Olsson, Anders Henrik (author)
- Copenhagen University Hospital
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- Ahlers, Juliane Maria Dorothee (author)
- Copenhagen University Hospital
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- Hansen, Ninna Schiøler (author)
- Copenhagen University Hospital,University of Copenhagen
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- Schrölkamp, Maren (author)
- Copenhagen University Hospital
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- Gillberg, Linn (author)
- Copenhagen University Hospital
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- Perfilyev, Alexander (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
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- Volkov, Petr (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
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- Jørgensen, Sine W. (author)
- Steno Diabetes Center Copenhagen
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- Mortensen, Brynjulf (author)
- Steno Diabetes Center Copenhagen
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- Hingst, Janne (author)
- University of Copenhagen
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- Wojtaszewski, Jørgen (author)
- University of Copenhagen
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- Scheele, Camilla (author)
- Copenhagen University Hospital,University of Copenhagen
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- Brøns, Charlotte (author)
- Copenhagen University Hospital
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- Pedersen, Bente Klarlund (author)
- University of Copenhagen
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- Vaag, Allan (author)
- Copenhagen University Hospital,AstraZeneca, Sweden,University of Copenhagen
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(creator_code:org_t)
- 2019-09-30
- 2020
- English 14 s.
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In: Endocrine Research. - : Informa UK Limited. - 0743-5800 .- 1532-4206. ; 45:1, s. 58-71
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- Background: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells. Results: Muscle progenitor cells were obtained from 23 healthy young adult men born at term with LBW, and 15 BMI-matched normal birth weight (NBW) controls. The cells were subsequently cultured and differentiated into myotubes. DNA and RNA were harvested before and after differentiation for genome-wide DNA methylation and RNA expression measurements. After correcting for multiple comparisons (q ≤ 0.05), 56 CpG sites were found to be significantly, differentially methylated in myoblasts from LBW compared with NBW men, of which the top five gene-annotated CpG sites (SKI, ARMCX3, NR5A2, NEUROG, ESRRG) previously have been associated to regulation of cholesterol, fatty acid and glucose metabolism and muscle development or hypertrophy. LBW men displayed markedly decreased myotube gene expression levels of the AMPK-repressing tyrosine kinase gene FYN and the histone deacetylase gene HDAC7. Silencing of FYN and HDAC7 was associated with impaired myotube formation, which for HDAC7 reduced muscle glucose uptake. Conclusions: The data provides evidence of impaired muscle development predisposing LBW individuals to T2D is linked to and potentially caused by distinct DNA methylation and transcriptional changes including down regulation of HDAC7 and FYN in their immature myoblast stem cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- epigenetics
- FAM8A1
- FYN
- HDAC7
- Low birth weight
- myogenesis
- skeletal muscle
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Broholm, Christa
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Ribel-Madsen, Ra ...
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Hjort, Line
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Olsson, Anders H ...
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Ahlers, Juliane ...
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Hansen, Ninna Sc ...
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show more...
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Schrölkamp, Mare ...
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Gillberg, Linn
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Perfilyev, Alexa ...
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Volkov, Petr
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Ling, Charlotte
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Jørgensen, Sine ...
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Mortensen, Brynj ...
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Hingst, Janne
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Wojtaszewski, Jø ...
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Scheele, Camilla
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Brøns, Charlotte
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Pedersen, Bente ...
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Vaag, Allan
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Endocrine Resear ...
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Lund University