Integrative genome-wide DNA methylome and transcriptome data reveals key genes involved in the dysregulation of adipose-stem cells linked to Crohn’s disease [Array]

Creeping fat, also known as mesenteric fat, which is connected to the inflamed segments of the intestine and is a hallmark of Crohn's disease (CD), appears to be correlated with disease activity. Adipose-stem cells isolated from the creeping fat of CD subjects were found to be dysfunctional (exhibiting a high inflammatory profile, high invasive and phagocytic capacities, and worse immunosuppressive properties), and this dysfunction persisted in hASCs taken from CD subjects who were in remission of the disease. We hypothesized that the abnormal behavior of adipose stem cells is caused by the accumulation of epigenetic modifications due to the inflammatory environment underlying active CD. DNA methylation and transcriptomics were performed in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue biopsies of active and inactive CD patients and non-IBD patients. An integrative analysis of both omics was performed to obtain the best gene candidates. Genomic DNA extracted from human adipocyte stem cells (hASCs) derived 18 Crohn’s disease (CD) patients samples and 7 healthy individual samples were analyzed with Human Methylation EPIC Infinium assay beadarrays to profile 850,000 sites in the human genome. CD samples were derived from different tissues and disease states: 6 creeping fat samples from active Crohn’s disease (CF_aCD), 7 mesenteric samples from active Crohn’s disease (hMES_aCD), and 5 mesenteric samples from inactive Crohn’s disease (hMES_iCD).