Fig. 5: Beta cells exhibit accelerated DNA demethylation in T2D (part I).
From: Epigenetic adaptation of beta cells across lifespan and disease
a, PCA of DNAm in beta cells from CTL and T2D donors. Boxplots of the PC1 stratified by condition for 12 CTL and seven T2D donors. Boxplot parameters: middle line, median; box upper (resp. lower) bound, 3rd (resp. 1st) quartile; upper/lower whisker extends to the largest/smallest value within 1.5× IQR; each donor is represented by a point. Asterisk indicates a two-sided Wilcoxon P < 0.05 (P = 0.03 in this case). b, Methylation scatterplot. Smooth scatterplot of beta cell methylation (%) in T2D versus CTL donors across 9,296 DMRs (FDR < 0.05, |delta| > 5%), illustrating subtle hypomethylation in T2D. c, Effect size distribution. Distribution of average methylation differences (T2D – CTL) for the DMRs shown in b. x axis, % difference (T2D – CTL); y axis, number of DMRs per bin. d,e, Enrichment heatmaps. Enrichment plot of signals from islet histone marks (d) and chromatin accessibility (snATAC-Seq, beta cells) and TF binding (ChIP-seq, whole islets) (e) across 9,296 DMRs (FDR < 0.05, |delta | >5%) from the T2D versus CTL beta cell comparison. Each row shows the signal over the 10 kb region centred at one DMR. Top, regions hypomethylated in T2D; bottom, hypomethylated in CTL beta cells. f, Gene set enrichment results. Gene set enrichment for hypomethylated DMRs based on DMR-distal genes (FDR < 0.05, |delta| > 10%) from the T2D versus CTL beta cell comparison. The x axis displays −log10 of the unadjusted P values from a one-sided hypergeometric test.
