Colonic epithelial cell diversity in health and inflammatory bowel disease.

Paper Info

Title
Colonic epithelial cell diversity in health and inflammatory bowel disease.

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.

Authors (22 rows)

Cited by (0 rows)

References (5 rows)

Name	Order	Citations	PageRank
Kaushal Parikh	1	0	0.34
Agne Antanaviciute	2	0	0.34
David Fawkner-Corbett	3	0	0.34
Marta Jagielowicz	4	0	0.34
Anna Aulicino	5	0	0.34
Christoffer Lagerholm	6	0	0.34
Simon Davis	7	0	0.34
James Kinchen	8	0	0.34
Hannah H Chen	9	0	0.34
Nasullah Khalid Alham	10	0	0.34
Neil Ashley	11	0	0.34
Errin Johnson	12	0	0.34
Philip Hublitz	13	0	0.34
Leyuan Bao	14	0	0.34
Joanna Lukomska	15	0	0.34
Rajinder Singh Andev	16	0	0.34
Elisabet Björklund	17	0	0.34
Benedikt M. Kessler	18	2	0.89
Roman Fischer	19	0	0.34
Robert Goldin	20	0	0.68
Hashem Koohy	21	0	0.68
Alison Simmons	22	1	0.69