The following is a summary of “Genome-wide DNA methylome and transcriptome profiling reveals key genes involved in the dysregulation of adipose-stem cells in Crohn’s disease,” published in the May 2024 issue of Gastroenterology by Monfort-Ferre et al.
Patients with Crohn’s disease (CD) exhibit expansion of mesenteric adipose tissue (MAT), also known as creeping fat (CF), containing highly pro-inflammatory adipose-stem cells (ASCs).
Researchers started a retrospective study identifying epigenetic modifications in dysfunctional ASCs of patients with CD, hypothesizing that chronic inflammation drives changes and contributes to disease progression.
They conducted genome-wide profiling of DNA methylome and transcriptome in ASCs isolated from MAT adipose tissue biopsies of patients with active and inactive CD and non-CD. With a validation cohort, main candidate genes were assessed via qPCR in various fat depots and immune cells.
The results showed disparities in DNA methylation and gene expression between ASCs from patients with CD and non-CD, with no activity-related differences observed. Pathway enrichment analysis highlighted significant enrichment of oxidative stress and immune response in active CD, with MAB21L2 identified as the most impacted gene. Validation analysis confirmed elevated MAB21L2 expression in MAT and adipose tissue macrophages in active CD. Additionally, a robust association was found between CACNA1H expression and disease remission, as it was higher in ASCs and MAT from patients with inactive CD, correlating negatively with C-reactive protein in peripheral blood mononuclear cells.
Investigators concluded that dysregulation in ASC of patients with CD likely involved epigenetic modifications, with MAB21L2 potentially linked to disease and CACNA1H potentially associated with remission.
Source: academic.oup.com/ecco-jcc/advance-article-abstract/doi/10.1093/ecco-jcc/jjae072/7673805