Additional file of The Role of Serrated Epithelial Cell Subpopulations in Colorectal Cancer Progression: Insights from Single-Cell Transcriptomics and Mendelian Randomization
Description
Colorectal cancer (CRC) is a complex disease involving diverse cellular populations and intricate gene regulatory networks. The role of serrated epithelial cell subpopulations in CRC progression remains unclear. This study utilized single-cell RNA sequencing to identify and characterize epithelial cell subpopulations, focusing on serrated cells in sessile serrated lesions (SSA/P). By integrating genome-wide association study (GWAS) data with single-cell transcriptomic data, Mendelian randomization analyses were performed to establish causal links between gene expression patterns in serrated cells and CRC risk. Key findings include a strong association between increased serrated cell populations and CRC onset, with gene-specific analysis highlighting IER3 as a potential driver of malignancy through pathways involving cell proliferation, adhesion, and immune evasion. Functional analyses further identified several genetic loci associated with serrated cell gene expression and validated their connections to CRC susceptibility. These findings underscore the critical role of serrated epithelial cells, particularly through genes like IER3, in CRC pathogenesis. This work provides novel insights into the molecular mechanisms underlying CRC and suggests potential biomarkers and therapeutic targets for future precision medicine approaches. Further studies are warranted to evaluate the translational potential of these discoveries.