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

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 po...

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Main Authors: 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, Sebastian Pott
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56212-2
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author 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
Sebastian Pott
author_facet 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
Sebastian Pott
author_sort Yu Zhao
collection DOAJ
description 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.
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spelling doaj-art-113cd4564391427f9da4fabf290fe6d02025-01-26T12:41:22ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-56212-2Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patientsYu Zhao0Ran Zhou1Bingqing Xie2Cambrian Y. Liu3Martin Kalski4Candace M. Cham5Zhiwei Jiang6Jason Koval7Christopher R. Weber8David T. Rubin9Mitch Sogin10Sean Crosson11Mengjie Chen12Jun Huang13Aretha Fiebig14Sushila Dalal15Eugene B. Chang16Anindita Basu17Sebastian Pott18University of Chicago, Pritzker School of Molecular EngineeringUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of ChemistryUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of PathologyUniversity of Chicago, Department of MedicineMarine Biological LaboratoryMichigan State UniversityUniversity of Chicago, Department of MedicineUniversity of Chicago, Pritzker School of Molecular EngineeringMichigan State UniversityUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineUniversity of Chicago, Department of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-56212-2
spellingShingle 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
Sebastian Pott
Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
Nature Communications
title Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
title_full Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
title_fullStr Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
title_full_unstemmed Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
title_short Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
title_sort multiomic analysis reveals cellular transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
url https://doi.org/10.1038/s41467-025-56212-2
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