Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines

Exposure to proinflammatory cytokines is believed to contribute to pancreatic ß-cells during diabetes development. While some cytokine-mediated changes in islet gene expression are known, the heterogeneity of the response is not well-understood. Following 6 hour treatment with interleukin-1 beta (IL-1ß) and interferon-gamma (IFN-?) alone or together, mouse islets were subjected to single-cell RNA-sequencing (scRNA-seq). Inducible nitric oxide synthase (iNOS) mRNA (Nos2), antiviral genes, and immune-associated genes were induced in a subset of ß-cells in response to both cytokines, while IL-1ß alone activated only antiviral genes. Subsets of a- and d-cells expressed Nos2 and exhibited similar gene expression changes as ß-cells, including induction of antiviral genes and repression of identity genes. Finally, cytokine-responsiveness was inversely correlated with expression of genes encoding heat shock proteins. Our findings show that all endocrine cell types respond to cytokines, IL-1ß induces the expression of protective genes in ß-cells, and cellular stress gene expression is associated with an inhibition in cytokine signaling. Overall design: Four samples of murine islets (no cytokine treatment, IL-1B only, IFNg only, IL-1B and IFNg exposure for 6 hours) were prepared using 10x Genomics Chromium platform