Epigenetic programming of adipose-derived stem cells in low birthweight individuals View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Christa Broholm, Anders H. Olsson, Alexander Perfilyev, Ninna S. Hansen, Maren Schrölkamp, Klaudia S. Strasko, Camilla Scheele, Rasmus Ribel-Madsen, Brynjulf Mortensen, Sine W. Jørgensen, Charlotte Ling, Allan Vaag

ABSTRACT

AIMS/HYPOTHESIS: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals. METHODS: ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men. The adipocytes were cultured in vitro, and genome-wide differences in RNA expression and DNA methylation profiles were analysed in ADSCs and differentiated adipocytes. RESULTS: We demonstrated that ADSCs from LBW individuals exhibit multiple expression changes as well as genome-wide alterations in methylation pattern. Reduced expression of the transcription factor cyclin T2 encoded by CCNT2 may play a key role in orchestrating several of the gene expression changes in ADSCs from LBW individuals. Indeed, silencing of CCNT2 in human adipocytes decreased leptin secretion as well as the mRNA expression of several genes involved in adipogenesis, including MGLL, LIPE, PPARG, LEP and ADIPOQ. Only subtle genome-wide mRNA expression and DNA methylation changes were seen in mature cultured adipocytes from LBW individuals. CONCLUSIONS/INTERPRETATION: Epigenetic and transcriptional changes in LBW individuals are most pronounced in immature ADSCs that in turn may programme physiological characteristics of the mature adipocytes that influence the risk of metabolic diseases. Reduced expression of CCNT2 may play a key role in the developmental programming of adipose tissue. More... »

PAGES

2664-2673

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-016-4099-9

DOI

http://dx.doi.org/10.1007/s00125-016-4099-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014939416

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27627980


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