IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56212-2.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56212-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56212-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    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. 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.
    4. 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.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Bárbara Andrade Barbosa & Saskia D. Asten & Ji Won Oh & Arantza Farina-Sarasqueta & Joanne Verheij & Frederike Dijk & Hanneke W. M. Laarhoven & Bauke Ylstra & Juan J. Garcia Vallejo & Mark A. Wiel & Y, 2021. "Bayesian log-normal deconvolution for enhanced in silico microdissection of bulk gene expression data," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Yuyao Liu & Zhen Li & Xiaoyang Chen & Xuejian Cui & Zijing Gao & Rui Jiang, 2025. "INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    5. Susanne Kessler & Bradly Burke & Geoffroy Andrieux & Jan Schinköthe & Lea Hamberger & Johannes Kacza & Shijun Zhan & Clara Reasoner & Taru S. Dutt & Maria Kaukab Osman & Marcela Henao-Tamayo & Julian , 2024. "Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Aaron T L Lun & Hervé Pagès & Mike L Smith, 2018. "beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types," PLOS Computational Biology, Public Library of Science, vol. 14(5), pages 1-15, May.
    7. Reza Mirzazadeh & Zaneta Andrusivova & Ludvig Larsson & Phillip T. Newton & Leire Alonso Galicia & Xesús M. Abalo & Mahtab Avijgan & Linda Kvastad & Alexandre Denadai-Souza & Nathalie Stakenborg & Ale, 2023. "Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Chang Su & Zichun Xu & Xinning Shan & Biao Cai & Hongyu Zhao & Jingfei Zhang, 2023. "Cell-type-specific co-expression inference from single cell RNA-sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Chengchen Zhao & Sheng’en Hu & Xiao Huo & Yong Zhang, 2017. "Dr.seq2: A quality control and analysis pipeline for parallel single cell transcriptome and epigenome data," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-14, July.
    10. Reta Birhanu Kitata & Marija Velickovic & Zhangyang Xu & Rui Zhao & David Scholten & Rosalie K. Chu & Daniel J. Orton & William B. Chrisler & Tong Zhang & Jeremy V. Mathews & Benjamin M. Bumgarner & D, 2025. "Robust collection and processing for label-free single voxel proteomics," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    11. Akshaya Ramakrishnan & Aikaterini Symeonidi & Patrick Hanel & Katharina T. Schmid & Maria L. Richter & Michael Schubert & Maria Colomé-Tatché, 2023. "epiAneufinder identifies copy number alterations from single-cell ATAC-seq data," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    12. Bokai Zhu & Yunhao Bai & Yao Yu Yeo & Xiaowei Lu & Xavier Rovira-Clavé & Han Chen & Jason Yeung & Dingani Nkosi & Jonathan Glickman & Antonio Delgado-Gonzalez & Georg K. Gerber & Mike Angelo & Alex K., 2025. "A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    13. Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    14. Ruohan Wang & Yumin Zheng & Zijian Zhang & Kailu Song & Erxi Wu & Xiaopeng Zhu & Tao P. Wu & Jun Ding, 2024. "MATES: a deep learning-based model for locus-specific quantification of transposable elements in single cell," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    15. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Egle Kvedaraite & Magda Lourda & Natalia Mouratidou & Tim Düking & Avinash Padhi & Kirsten Moll & Paulo Czarnewski & Indranil Sinha & Ioanna Xagoraris & Efthymia Kokkinou & Anastasios Damdimopoulos & , 2024. "Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Suhas V. Vasaikar & Adam K. Savage & Qiuyu Gong & Elliott Swanson & Aarthi Talla & Cara Lord & Alexander T. Heubeck & Julian Reading & Lucas T. Graybuck & Paul Meijer & Troy R. Torgerson & Peter J. Sk, 2023. "A comprehensive platform for analyzing longitudinal multi-omics data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Maja Olecka & Alena Bömmel & Lena Best & Madlen Haase & Silke Foerste & Konstantin Riege & Thomas Dost & Stefano Flor & Otto W. Witte & Sören Franzenburg & Marco Groth & Björn Eyss & Christoph Kaleta , 2024. "Nonlinear DNA methylation trajectories in aging male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Xueyan Wu & Hui Ying & Qianqian Yang & Qian Yang & Haoyu Liu & Yilan Ding & Huiling Zhao & Zhihe Chen & Ruizhi Zheng & Hong Lin & Shuangyuan Wang & Mian Li & Tiange Wang & Zhiyun Zhao & Min Xu & Yuhon, 2024. "Transcriptome-wide Mendelian randomization during CD4+ T cell activation reveals immune-related drug targets for cardiometabolic diseases," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56212-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.