Dataset Information

Single-cell census of the colonic epithelium reveals goblet cell drivers of barrier breakdown in inflammatory bowel disease

ABSTRACT: Colonic epithelial cells facilitate host-microbe interactions to control mucosal immunity, and they also coordinate recycling and forming the mucus barrier. Epithelial barrier breakdown underpins inflammatory bowel disease (IBD). However, we do not know the specific contributions of each epithelial cell subtype to this process. Here, we profiled single colonic epithelial cells in health and IBD. Our results identified previously unknown subtypes and crypt gradients of progenitors, colonocytes and goblet cells. We also revealed a novel specialized metal ion storage and chloride secretory cell. In IBD, we discovered a unique cluster of disease associated goblet cells that remodels the barrier. We found downregulated WFDC2, a novel goblet cell expressing anti-protease that inhibited bacterial growth. Our in vivo studies demonstrated WFDC2 preserved tight junction integrity and prevented commensal invasion and mucosal inflammation. We delineate markers and transcriptional states, identify a new colonic epithelial cell and uncover fundamental principles of epithelial plasticity and barrier breakdown in IBD. Thus, our study reveals new therapeutic targets and disease-related mechanisms in IBD

OTHER RELATED OMICS DATASETS IN: GSE116222

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Inflammatory Bowel Disease

SUBMITTER: Simon Davis

LAB HEAD: Roman Fischer

PROVIDER: PXD011655 | Pride | 2019-02-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	FL994_MSQ1484_20180910_DFawknerCorbett.MSMS.mgf	Mgf
	FL994_MSQ1484_20180910_DFawknerCorbett.mzid.gz	Mzid
	FL994_MSQ1484_20180910_DFawknerCorbett_1.raw	Raw
	FL994_MSQ1484_20180910_DFawknerCorbett_2.raw	Raw
	FL994_MSQ1484_20180910_DFawknerCorbett_3.raw	Raw

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Publications

Colonic epithelial cell diversity in health and inflammatory bowel disease.

Parikh Kaushal K Antanaviciute Agne A Fawkner-Corbett David D Jagielowicz Marta M Aulicino Anna A Lagerholm Christoffer C Davis Simon S Kinchen James J Chen Hannah H HH Alham Nasullah Khalid NK Ashley Neil N Johnson Errin E Hublitz Philip P Bao Leyuan L Lukomska Joanna J Andev Rajinder Singh RS Björklund Elisabet E Kessler Benedikt M BM Fischer Roman R Goldin Robert R Koohy Hashem H Simmons Alison A

Nature 20190227 7746

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 pr ...[more]

PMID: 30814735

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