Journal Article

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

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

2016

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adipocytes / Adipocytes - metabolism / Adipogenesis - genetics / Adiponectin - genetics / Adipose Tissue - cytology / Adipose Tissue - metabolism / Adult / Adults / Basic Medicine / Biopsy / Birth weight / Birth Weight - genetics / Birth Weight - physiology / Body fat / Cell and Molecular Biology / Cell- och molekylärbiologi / Cells, Cultured / Cyclin T - genetics / Diabetes / DNA methylation / DNA Methylation - genetics / Epigenesis, Genetic - genetics / Epigenetics / Gene expression / Genomes / Human Physiology / Humans / Internal Medicine / Male / Medical and Health Sciences / Medicin och hälsovetenskap / Medicine / Medicine & Public Health / Medicinska och farmaceutiska grundvetenskaper / Metabolic Diseases / Metabolic disorders / Real-Time Polymerase Chain Reaction / RNA, Small Interfering - genetics / STAT2 Transcription Factor - genetics / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Young Adult