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

Abstract

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, the cell type-specific miRNome during UC remains unknown. Thus, we aimed to explore miRNA expression patterns in colon tissue and epithelial cells during 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, and gene-set enrichment analyses. Results Differentially expressed colonic tissue miRNAs showed potential involvement in the regulation of interleukin-4 [IL-4] and IL-13 signalling during UC. As this pathway plays a 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 under 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 was significantly enriched in 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.