Spatial transcriptomics reveals unique inflammatory signatures across all anatomic locations in post-operative crohn's disease.
Academic Article
Overview
abstract
BACKGROUND AND AIMS: Most patients with Crohn's disease (CD) who have undergone ileocolonic resection experience recurrent inflammation within one year after surgery. We examined the molecular basis underlying gastrointestinal inflammation in post-operative CD across 3 common anatomic locations of recurrence. METHODS: To characterise spatial transcriptomic signatures, this study utilised biopsies from the colon, neo-terminal ileum, and anastomosis of patients with post-operative CD in the PREDICT-OR study. Sample analyses were performed with 10X Genomics Visium CytAssist system V2.0, and data analyses with R. RESULTS: Histologically inflamed biopsies from all locations shared transcriptional signatures across 3 cellular niches (myeloid, B, T cells) and a specialised epithelial cell type expressing inflammation-associated genes. Differentially expressed genes overexpressed inflammatory pathway activity across the 3 locations, whereas hypoxic pathways were less apparent. In addition to genes for known treatment targets, epidermal growth factor receptor and mitogen-activated protein kinase pathways were upregulated. Cellular niches shaped inflammatory microenvironments through endoplasmic reticulum stress and extracellular matrix remodelling signalling. CONCLUSIONS: Application of spatial transcriptomics revealed a common disease signature for post-operative CD across the colon, neo-terminal ileum, and anastomosis. Inflamed biopsies from all locations demonstrated similar immune cell and inflammatory gene expression patterns as opposed to hypoxic pathways, and unique inflammatory pathways were revealed.
