Integrated Single-cell and Bulk RNA Sequencing Reveals CREM is Involved in the Pathogenesis of Ulcerative Colitis

Background: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by persistent colonic inflammation. Here, we performed a systematic analysis to gain better insights into UC pathogenesis.

Methods: We analyzed two UC-related datasets extracted from the gene expression omnibus database using several bioinformatics tools. The primary cell types and key subgroups of primary cells associated with UC and differentially expressed genes (DEGs) between UC and control samples were identified. The molecular regulation of the key genes was also predicted. The gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses of marker genes of key cell subgroups and model genes were performed. The expression of key enriched genes was validated in 10 clinical samples using real-time quantitative polymerase chain reaction (RT-qPCR).

Results: Monocytes were identified as the major cell type. Ten differentially expressed marker genes were obtained by intersecting the 3121 DEGs, 38 marker genes in major cell types, and 104 marker genes in key cell subgroups. Four essential genes, associated with immune response, were obtained using support vector machine recursive feature elimination and least absolute shrinkage and selection operator analyses. The four essential genes were highly expressed in Cluster 0 during differentiation. Validation of the four key genes in colonic mucosal biopsy specimens from 10 normal and 10 UC patients revealed that was highly expressed in both the lesion-free sites and lesion sites colonic mucosa of UC patients compared with normal adults.

Conclusions: We identified involved in UC pathogenesis, which is expected to provide a new therapeutic target for UC.