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

Author

Listed:
  • 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
    Department of Pathology)

  • 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)

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.

Suggested Citation

  • 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 &, 2025. "Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56212-2
    DOI: 10.1038/s41467-025-56212-2
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    References listed on IDEAS

    as
    1. Rasa Elmentaite & Natsuhiko Kumasaka & Kenny Roberts & Aaron Fleming & Emma Dann & Hamish W. King & Vitalii Kleshchevnikov & Monika Dabrowska & Sophie Pritchard & Liam Bolt & Sara F. Vieira & Lira Mam, 2021. "Cells of the human intestinal tract mapped across space and time," Nature, Nature, vol. 597(7875), pages 250-255, September.
    2. John W. Hickey & Winston R. Becker & Stephanie A. Nevins & Aaron Horning & Almudena Espin Perez & Chenchen Zhu & Bokai Zhu & Bei Wei & Roxanne Chiu & Derek C. Chen & Daniel L. Cotter & Edward D. Espli, 2023. "Organization of the human intestine at single-cell resolution," Nature, Nature, vol. 619(7970), pages 572-584, July.
    3. Jason D. Buenrostro & Beijing Wu & Ulrike M. Litzenburger & Dave Ruff & Michael L. Gonzales & Michael P. Snyder & Howard Y. Chang & William J. Greenleaf, 2015. "Single-cell chromatin accessibility reveals principles of regulatory variation," Nature, Nature, vol. 523(7561), pages 486-490, July.
    4. Xuran Wang & Jihwan Park & Katalin Susztak & Nancy R. Zhang & Mingyao Li, 2019. "Bulk tissue cell type deconvolution with multi-subject single-cell expression reference," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    5. Jia Li & Alan J. Simmons & Caroline V. Hawkins & Sophie Chiron & Marisol A. Ramirez-Solano & Naila Tasneem & Harsimran Kaur & Yanwen Xu & Frank Revetta & Paige N. Vega & Shunxing Bao & Can Cui & Regin, 2024. "Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
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