Background: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Previous single-cell transcriptomic studies have mostly focused on established disease, leaving a knowledge gap in relation to treatment-naive profiles across multiple regions of the gut.
Methods: To study disease onset, a treatment-naive pediatric CD cohort was recruited, and single-cell transcriptomics was performed on ileum, colon, and rectum biopsies collected at initial endoscopy. A clustering stability assessment workflow was developed to ensure clustering and downstream results were robust.
Results: Inflammation did not strongly influence cellular proportion due to heterogeneity across donor and tissue. Tensor decomposition revealed distinct mesenchymal and myeloid cell-mediated sources of disease pathology, corresponding to previously identified fibrotic and pro-inflammatory disease progression. Integrating transcriptomics and genome-wide association summary statistics for CD suggested myeloid and T cells drive disease, highlighting potential cellular therapeutic targets.
Conclusion: Tensor decomposition stratified donors into clinically meaningful groups based on their transcriptomic profile, suggesting these signatures can be utilized for personalized medicine.
Keywords: RNA-seq; pathology; single-cell.
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