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Colonic epithelial cell diversity in health and inflammatory bowel disease

Author

Listed:
  • Kaushal Parikh

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Agne Antanaviciute

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital
    John Radcliffe Hospital, University of Oxford)

  • David Fawkner-Corbett

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital
    John Radcliffe Hospital, University of Oxford)

  • Marta Jagielowicz

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Anna Aulicino

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Christoffer Lagerholm

    (MRC Weatherall Institute of Molecular Medicine)

  • Simon Davis

    (University of Oxford)

  • James Kinchen

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Hannah H. Chen

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Nasullah Khalid Alham

    (John Radcliffe Hospital, University of Oxford)

  • Neil Ashley

    (John Radcliffe Hospital, University of Oxford)

  • Errin Johnson

    (University of Oxford)

  • Philip Hublitz

    (John Radcliffe Hospital, University of Oxford)

  • Leyuan Bao

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Joanna Lukomska

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Rajinder Singh Andev

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Elisabet Björklund

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

  • Benedikt M. Kessler

    (University of Oxford)

  • Roman Fischer

    (University of Oxford)

  • Robert Goldin

    (St Mary’s Hospital, Imperial College)

  • Hashem Koohy

    (John Radcliffe Hospital, University of Oxford)

  • Alison Simmons

    (John Radcliffe Hospital, University of Oxford
    John Radcliffe Hospital)

Abstract

The colonic epithelium facilitates host–microorganism interactions to control mucosal immunity, coordinate nutrient recycling and form a mucus barrier. Breakdown of the epithelial barrier underpins inflammatory bowel disease (IBD). However, the specific contributions of each epithelial-cell subtype to this process are unknown. Here we profile single colonic epithelial cells from patients with IBD and unaffected controls. We identify previously unknown cellular subtypes, including gradients of progenitor cells, colonocytes and goblet cells within intestinal crypts. At the top of the crypts, we find a previously unknown absorptive cell, expressing the proton channel OTOP2 and the satiety peptide uroguanylin, that senses pH and is dysregulated in inflammation and cancer. In IBD, we observe a positional remodelling of goblet cells that coincides with downregulation of WFDC2—an antiprotease molecule that we find to be expressed by goblet cells and that inhibits bacterial growth. In vivo, WFDC2 preserves the integrity of tight junctions between epithelial cells and prevents invasion by commensal bacteria and mucosal inflammation. We delineate markers and transcriptional states, identify a colonic epithelial cell and uncover fundamental determinants of barrier breakdown in IBD.

Suggested Citation

  • Kaushal Parikh & Agne Antanaviciute & David Fawkner-Corbett & Marta Jagielowicz & Anna Aulicino & Christoffer Lagerholm & Simon Davis & James Kinchen & Hannah H. Chen & Nasullah Khalid Alham & Neil As, 2019. "Colonic epithelial cell diversity in health and inflammatory bowel disease," Nature, Nature, vol. 567(7746), pages 49-55, March.
  • Handle: RePEc:nat:nature:v:567:y:2019:i:7746:d:10.1038_s41586-019-0992-y
    DOI: 10.1038/s41586-019-0992-y
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    Cited by:

    1. Ziyu Liang & Courtney E. Wilson & Bochuan Teng & Sue C. Kinnamon & Emily R. Liman, 2023. "The proton channel OTOP1 is a sensor for the taste of ammonium chloride," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Yue Wang & Yanbo Yu & Lixiang Li & Mengqi Zheng & Jiawei Zhou & Haifan Gong & Bingcheng Feng & Xiao Wang & Xuanlin Meng & Yanyan Cui & Yanan Xia & Shuzheng Chu & Lin Lin & Huijun Chang & Ruchen Zhou &, 2023. "Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Elvira Mennillo & Yang Joon Kim & Gyehyun Lee & Iulia Rusu & Ravi K. Patel & Leah C. Dorman & Emily Flynn & Stephanie Li & Jared L. Bain & Christopher Andersen & Arjun Rao & Stanley Tamaki & Jessica T, 2024. "Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Alba Garrido-Trigo & Ana M. Corraliza & Marisol Veny & Isabella Dotti & Elisa Melón-Ardanaz & Aina Rill & Helena L. Crowell & Ángel Corbí & Victoria Gudiño & Miriam Esteller & Iris Álvarez-Teubel & Da, 2023. "Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease," Nature Communications, Nature, vol. 14(1), pages 1-18, 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.
    6. Jiacheng Wu & Xiaoqing Xu & Jiaqi Duan & Yangyang Chai & Jiaying Song & Dongsheng Gong & Bingjing Wang & Ye Hu & Taotao Han & Yuanyuan Ding & Yin Liu & Jingnan Li & Xuetao Cao, 2024. "EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. María A. Duque-Correa & David Goulding & Faye H. Rodgers & J. Andrew Gillis & Claire Cormie & Kate A. Rawlinson & Allison J. Bancroft & Hayley M. Bennett & Magda E. Lotkowska & Adam J. Reid & Annelies, 2022. "Defining the early stages of intestinal colonisation by whipworms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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