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. 2018 Feb;154(3):585–598. doi: 10.1053/j.gastro.2017.10.007

Figure 5.

Figure 5

Stability of disease-associated intestinal epithelial DNA methylation changes: (A) Correlation plot of DNA methylation (Beta values) of disease-associated differentially methylated positions (DMPs) at diagnosis and at repeat endoscopy for each patient at the 2 time points. Shown are Crohn’s disease (CD)-associated DMPs (left) and ulcerative colitis (UC)-associated DMPs (right) in sigmoid colon (SC) epithelium (adjusted P <. 01). (B) Brightfield microscopic images of fully grown intestinal epithelial organoids derived from 2 gut segments (ie, terminal ileum [TI] and SC) of CD and control patients. (C) Quantile-quantile plot generated from organoid-derived genome-wide DNAm P values. Plotted are P values (observed vs expected) comparing specific CD-associated DMPs (from Figure 3) for each gut segment with randomly selected CpGs. (D) Examples of CD-associated DMPs being retained in patient-derived organoids. Plotted are beta values derived from genome-wide array data generated from purified colonic epithelium and respective organoids. GREB1, Growth Regulation By Estrogen In Breast Cancer 1; TMEM173, Transmembrane Protein 173; PDE1B, Phosphodiesterase 1B; CtrlP, Control purified IEC (n = 14); CDP, CD purified IEC (n = 13); CtrlO, Control organoids (n = 7); CDO, CD organoids (n = 5). (E) Validation of CpGs shown in D. Validation of genome-wide DNAm data using pyrosequencing. n = 5–7 per group; *P < .05; ***P < .001; unpaired, 2-tailed t-test between Ctrl and CD.