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

Yu Zhao, Ran Zhou, Bingqing Xie, Cambrian Y. Liu, Martin Kalski, Candace M. Cham, Zhiwei Jiang, Jason Koval, Christopher R. Weber, David T. Rubin, Mitch Sogin, Sean Crosson, Mengjie Chen, Jun Huang, Aretha Fiebig, Sushila Dalal, Eugene B. Chang, Anindita Basu () and Sebastian Pott ()
Additional contact information
Yu Zhao: Pritzker School of Molecular Engineering
Ran Zhou: Department of Medicine
Bingqing Xie: Department of Medicine
Cambrian Y. Liu: Department of Medicine
Martin Kalski: Department of Medicine
Candace M. Cham: Department of Medicine
Zhiwei Jiang: Department of Chemistry
Jason Koval: Department of Medicine
Christopher R. Weber: Department of Pathology
David T. Rubin: Department of Medicine
Mitch Sogin: Marine Biological Laboratory
Sean Crosson: Michigan State University
Mengjie Chen: Department of Medicine
Jun Huang: Pritzker School of Molecular Engineering
Aretha Fiebig: Michigan State University
Sushila Dalal: Department of Medicine
Eugene B. Chang: Department of Medicine
Anindita Basu: Department of Medicine
Sebastian Pott: Department of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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 an additional population 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.

Date: 2025
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DOI: 10.1038/s41467-025-56212-2

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