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Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men

Broholm, Christa (författare)
Copenhagen University Hospital
Ribel-Madsen, Rasmus (författare)
Danish Diabetes Academy,Copenhagen University Hospital
Hjort, Line (författare)
University of Copenhagen,Copenhagen University Hospital
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Olsson, Anders Henrik (författare)
Copenhagen University Hospital
Ahlers, Juliane Maria Dorothee (författare)
Copenhagen University Hospital
Hansen, Ninna Schiøler (författare)
University of Copenhagen,Copenhagen University Hospital
Schrölkamp, Maren (författare)
Copenhagen University Hospital
Gillberg, Linn (författare)
Copenhagen University Hospital
Perfilyev, Alexander (författare)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
Volkov, Petr (författare)
Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
Ling, Charlotte (författare)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
Jørgensen, Sine W. (författare)
Steno Diabetes Center Copenhagen
Mortensen, Brynjulf (författare)
Steno Diabetes Center Copenhagen
Hingst, Janne (författare)
University of Copenhagen
Wojtaszewski, Jørgen (författare)
University of Copenhagen
Scheele, Camilla (författare)
Copenhagen University Hospital,University of Copenhagen
Brøns, Charlotte (författare)
Copenhagen University Hospital
Pedersen, Bente Klarlund (författare)
University of Copenhagen
Vaag, Allan (författare)
University of Copenhagen,Copenhagen University Hospital,AstraZeneca, Sweden
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Taylor & Francis, 2020
Engelska 14 s.
Ingår i: Endocrine Research. - : Taylor & Francis. - 0743-5800. ; 45:1, s. 58-71
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • 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.


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)


Low birth weight
skeletal muscle

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