Single‐cell analysis of Crohn's disease: Unveiling heterogeneity and evaluating ustekinumab outcomes

Abstract Background The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single‐cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue. Methods We applied scRNA‐sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein–protein interaction networks were constructed to identify crucial genes and pathways. Results Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level. Conclusions Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.