The microRNA expression in crypt-top and crypt-bottom colonic epithelial cell populations demonstrates cell-type specificity and correlates with endoscopic activity in ulcerative colitis

Ruta Inciuraite; Rima Ramonaite; Juozas Kupcinskas; Indre Dalgediene; Ugne Kulokiene; Vytautas Kiudelis; Greta Varkalaite; Aurelija Zvirbliene; Laimas Virginijus Jonaitis; Gediminas Kiudelis; Andre Franke; Stefan Schreiber; Simonas Juzenas; Jurgita Skieceviciene

doi:10.1093/ecco-jcc/jjae108

The microRNA expression in crypt-top and crypt-bottom colonic epithelial cell populations demonstrates cell-type specificity and correlates with endoscopic activity in ulcerative colitis

J Crohns Colitis. 2024 Jul 18:jjae108. doi: 10.1093/ecco-jcc/jjae108. Online ahead of print.

Authors

Ruta Inciuraite¹, Rima Ramonaite¹, Juozas Kupcinskas^{1

2}, Indre Dalgediene³, Ugne Kulokiene¹, Vytautas Kiudelis^{1

2}, Greta Varkalaite¹, Aurelija Zvirbliene³, Laimas Virginijus Jonaitis^{1

2}, Gediminas Kiudelis^{1

2}, Andre Franke⁴, Stefan Schreiber⁴, Simonas Juzenas^{1

3}, Jurgita Skieceviciene¹

Affiliations

¹ Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
² Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
³ Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
⁴ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.

PMID: 39022905
DOI: 10.1093/ecco-jcc/jjae108

Abstract

Background and aims: Colonic epithelial barrier dysfunction is one of the early events in ulcerative colitis (UC) and microRNAs (miRNAs) participate in its regulation. However, cell type-specific miRNome during UC is still unknown. Thus, we aimed to explore miRNA expression patterns in colon tissue and epithelial cells at active and quiescent UC.

Methods: Small RNA-sequencing in colon tissue, crypt-bottom (CD44+), and crypt-top (CD66a+) colonic epithelial cells from two cohorts of UC patients (n=74) and healthy individuals (n=50) was performed. Data analysis encompassed differential expression, weighted gene co-expression network, correlation, gene-set enrichment analyses.

Results: Differentially expressed colonic tissue miRNAs showed potential involvement in regulation of interleukin-4 and interleukin-13 signalling during UC. As this pathway plays role in intestinal barrier regulation, consecutive analysis of spatially distinct colonic epithelial cell populations was performed. Cell-type (crypt-top and crypt-bottom) specific miRNA expression patterns were identified in both active and quiescent UC. Target genes of differentially expressed epithelial miRNAs at different disease activity were overrepresented in epithelial cell migration and therefore intestinal barrier integrity regulation. The pro-inflammatory miRNA co-expression module M1 correlated with endoscopic disease activity and successfully distinguished active and quiescent UC not only in both epithelial cell populations, but also in the colon tissue. The anti-inflammatory module M2 was specific to crypt-bottom cells and significantly enriched in the quiescent UC patients.

Conclusions: miRNA expression was specific to colonic epithelial cell populations and UC state, reflecting endoscopic disease activity. Irrespective of the UC state, deregulated epithelial miRNAs were associated with regulation of intestinal barrier integrity.

Keywords: Colon crypt-bottom epithelial cells; Ulcerative colitis; colon crypt-top epithelial cells; microRNA.