Spatially-structured inflammatory response in the presence of a uniform stimulus

Abstract

Inflammatory responses occur within the complex spatial context of tissues and organs, and many questions remain about how tissue structure and cellular communication shape their spatiotemporal dynamics. Here, we use a multiplexed RNA in situ hybridization approach, together with analytical tools, to study inflammatory gene expression in the larval zebrafish tailfin in response to a bath of lipopolysaccharide (LPS). We use this model system to address whether spatial structure emerges in the tissue response even absent the spatial variation introduced by a pathogen. We find that epithelial cells in the tailfin express several pro-inflammatory genes, and that across these genes, the uniform stimulus triggers a spatially non-uniform response. We use a graph-based spectral decomposition method to analyze its structure, and find that long modes dominate, creating zones of activation. Overall, these zones account for a majority of the variation in gene expression. Our results show that epithelial cells are important producers of pro-inflammatory effector molecules in this system, and that tissue induces spatial correlations even absent a structured input.