RT Journal Article
SR Electronic
T1 Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 2069
OP 2079
DO 10.1136/gutjnl-2016-312609
VO 66
IS 12
A1 Dotti, Isabella
A1 Mora-Buch, Rut
A1 Ferrer-Picón, Elena
A1 Planell, Núria
A1 Jung, Peter
A1 Masamunt, M Carme
A1 Leal, Raquel Franco
A1 Martín de Carpi, Javier
A1 Llach, Josep
A1 Ordás, Ingrid
A1 Batlle, Eduard
A1 Panés, Julián
A1 Salas, Azucena
YR 2017
UL http://gut.bmj.com/content/66/12/2069.abstract
AB Objective 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.Design 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.Results 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, CLDN18 and LYZ). A high rate of concordance was found in the expression profiles of the organoid cultures and whole colonic tissues from patients with UC.Conclusions 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.