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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Nature Portfolio
2025-01-01
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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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id | doaj-art-113cd4564391427f9da4fabf290fe6d0 |
institution | Kabale University |
issn | 2041-1723 |
language | English |
publishDate | 2025-01-01 |
publisher | Nature Portfolio |
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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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