Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.

Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds previously uncharacterized populations of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including CEACAM5 and CD24. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.