Colonic epithelial cell diversity in health and inflammatory bowel disease

Kaushal Parikh, Agne Antanaviciute, David Fawkner-Corbett, Marta Jagielowicz, Anna Aulicino, Christoffer Lagerholm, Simon Davis, James Kinchen, Hannah H. Chen, Nasullah Khalid Alham, Neil Ashley, Errin Johnson, Philip Hublitz, Leyuan Bao, Joanna Lukomska, Rajinder Singh Andev, Elisabet Björklund, Benedikt M. Kessler, Roman Fischer, Robert Goldin, Hashem Koohy and Alison Simmons ()
Additional contact information
Kaushal Parikh: John Radcliffe Hospital, University of Oxford
Agne Antanaviciute: John Radcliffe Hospital, University of Oxford
David Fawkner-Corbett: John Radcliffe Hospital, University of Oxford
Marta Jagielowicz: John Radcliffe Hospital, University of Oxford
Anna Aulicino: John Radcliffe Hospital, University of Oxford
Christoffer Lagerholm: MRC Weatherall Institute of Molecular Medicine
Simon Davis: University of Oxford
James Kinchen: John Radcliffe Hospital, University of Oxford
Hannah H. Chen: John Radcliffe Hospital, University of Oxford
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
Joanna Lukomska: John Radcliffe Hospital, University of Oxford
Rajinder Singh Andev: John Radcliffe Hospital, University of Oxford
Elisabet Björklund: John Radcliffe Hospital, University of Oxford
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

Nature, 2019, vol. 567, issue 7746, 49-55

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-0992-y

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