Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory intestinal diseases that show a perplexing heterogeneity in manifestations and response to treatment. The molecular basis for this heterogeneity remains uncharacterized. We applied single-cell RNA sequencing and CosMxTM Spatial Molecular Imaging to human colon and found the highest diversity in cellular composition in the myeloid compartment of UC and CD patients.

Besides resident macrophage subsets (M0 and M2), patients showed a variety of activated macrophages including classical (M1 CXCL5 and M1 ACOD1) and new inflammation-dependent alternative (IDA) macrophages. In addition, we captured intestinal neutrophils in three transcriptional states. Subepithelial IDA macrophages expressed NRG1, which promotes epithelial differentiation. In contrast, NRG1low IDA macrophages were expanded within the submucosa and in granulomas, in proximity to abundant inflammatory fibroblasts, which we suggest may promote macrophage activation. We conclude that macrophages sense and respond to unique tissue microenvironments, potentially contributing to patient-to-patient heterogeneity.

Links to extra information:

Our full publication is here. You can inspect our scRNAseq dataset easily by using our ShinyApp here. You can explore the code for the analysis of HC/IBD samples on here website and the analyisis of all samples togehter in here. CosMx Spatial analyisis is available here. Raw data generated for this publication is available in GEO omnibus for single cell expression and CosMx Spatial analysis.


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