Spatial transcriptomic analysis of Yersinia pseudotuberculosis infected ileum reveals novel enterocyte transcriptional state and bacterial localization

Despite being impacted in Crohn’s disease and a major target for a range of infections, we know relatively little about the complexity of cellular responses and cell-cell communication in the ileum during infection. Single cell and spatial transcriptomics have emerged as powerful technologies to study tissue complexity in the gut, but these tools have focused on the large intestine, in part due to the accessibility of this tissue for biopsies and its importance in cancer.

Here we present GutPath, an atlas of over 500,000 single cells that captures RNA and protein expression profiles for 91 cell states in the ileum across a range of model infectionsdiverse infectious archetypes. We show that GutPath accurately captures established immune responses to infection while revealing pathogen-specific responses in enterocytes. To highlight the discovery potential of this atlas, we identify a novel enterocyte cell state present during Yersinia pseudotuberculosis infection that is spatially linked to bacterial load and tissue pathology.