PXD064643

PXD064643 is an original dataset announced via ProteomeXchange.

Title	Biopsy-derived colonoid monolayers reveal a range of persistent mucosal defects in patients with ulcerative colitis
Description	Rationale: Ulcerative colitis (UC) is characterized by colonic mucosal inflammation and barrier dysfunction. We hypothesize that UC causes persistent defects in mucosal homeostasis, evident even in the absence of inflammation, contributing to disease chronicity. Objective: To test this, we grew patient biopsy-derived sigmoid colonoids into air-liquid interface (ALI) monolayers, characterizing them through microscopy, proteomics, bulk RNAseq, and their susceptibility to UC patient-isolated Escherichia coli pathobiont p19A. Findings: Non-IBD ALI monolayers formed uniform crypt-like structures, mature goblet cells and a thick mucus layer containing all epithelial-derived proteins previously identified in human colonic mucus. In contrast, ALI monolayers from UC patients displayed a range of impairments, from distorted crypt-like structures and a thinner and more permeable mucus layer to severe defects in cellular differentiation and crypt development. Transcriptome analysis identified activated pathways associated with extracellular matrix formation and cell signaling, including numerous cancer-associated genes in UC ALI monolayers, which also proved significantly more susceptible to E. coli p19A. Conclusions: The culturing of patient biopsies into ALI colonoid monolayers provides a powerful model to assess human mucosal development, healing, homeostasis and mucus barrier function, revealing that UC-derived colonoids display a range of developmental and functional defects that persist in the absence of inflammation.
HostingRepository	PRIDE
AnnounceDate	2026-01-29
AnnouncementXML	Submission_2026-01-29_11:09:26.969.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominique Levesque
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 12:45:24	ID requested
⏵ 1	2026-01-29 11:09:27	announced

10.1093/IBD/IZAF318;

submitter keyword: Mucus, Air-liquid interface, Pathobiont,Ulcerative colitis, Mucosal homeostasis

Bruce A. Vallance
contact affiliation	Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
contact email	bvallance@cw.bc.ca
lab head
Dominique Levesque
contact affiliation	University of Sherbrooke, FM Boisvert lab
contact email	dominique.levesque@usherbrooke.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064643
     1. Label: PRIDE project
     2. Name: Biopsy-derived colonoid monolayers reveal a range of persistent mucosal defects in patients with ulcerative colitis