Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis.
UC is a chronic inflammatory disease of the colonic mucosa. Growing evidence supports a role for epithelial cell defects in driving pathology. Moreover, long-lasting changes in the epithelial barrier have been reported in quiescent UC. Our aim was to investigate whether epithelial cell defects could originate from changes in the epithelial compartment imprinted by the disease.



Epithelial organoid cultures (EpOCs) were expanded ex vivo from the intestinal crypts of non-IBD controls and patients with UC. EpOCs were induced to differentiate (d-EpOCs), and the total RNA was extracted for microarray and quantitative real-time PCR (qPCR) analyses. Whole intestinal samples were used to determine mRNA expression by qPCR, or protein localisation by immunostaining.



EpOCs from patients with UC maintained self-renewal potential and the capability to give rise to differentiated epithelial cell lineages comparable with control EpOCs. Nonetheless, a group of genes was differentially regulated in the EpOCs and d-EpOCs of patients with UC, including genes associated with antimicrobial defence (ie,LYZ,PLA2G2A), with secretory (ie,ZG16,CLCA1) and absorptive (ie,AQP8,MUC12) functions, and with a gastric phenotype (ie,ANXA10,CLDN18andLYZ). A high rate of concordance was found in the expression profiles of the organoid cultures and whole colonic tissues from patients with UC.



Permanent changes in the colonic epithelium of patients with UC could be promoted by alterations imprinted in the stem cell compartment. These changes may contribute to perpetuation of the disease.
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Isabella
I
Dotti
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Rut
R
Mora-Buch
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Elena
E
Ferrer-Picón
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.|Bioinformatics Platform, CIBERehd, Barcelona, Spain.
Núria
N
Planell
Oncology Program, Institute for Research in Biomedicine (IRB), Barcelona, Spain.|German Cancer Consortium (DKTK), Heidelberg, Germany.
Peter
P
Jung
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
M Carme
MC
Masamunt
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.|IBD Research Laboratory, Surgery Department, Universidade Estadual de Campinas, Campinas, Sao Paulo, Brazil.
Raquel Franco
RF
Leal
Department of Gastroenterology, Hepatology and Pediatric Nutrition, Hospital Sant Joan de Deu, Barcelona, Spain.
Javier
J
Martín de Carpi
Endoscopy Unit, Hospital Clínic, CIBERehd, Barcelona, Spain.
Josep
J
Llach
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Ingrid
I
Ordás
Oncology Program, Institute for Research in Biomedicine (IRB), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Eduard
E
Batlle
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Julián
J
Panés
Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Azucena
A
Salas
D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
D012313:RNA
GENE EXPRESSION; INTESTINAL EPITHELIUM; STEM CELLS; ULCERATIVE COLITIS