An early islet transcriptional signature drives local inflammation in autoimmune diabetes

Pancreatic islet cell populations in KRV-infected LEW.1WR1 rats compared to those of controls identifies a population of "hot" endocrine cells that appear to lead to autoimmume diabetes in the infected rats. Overall design: Pancreatic islet cells were extracted from LEW.1WR1 rats on Day 11 post-treatment under three conditions - PBS (no-treatment control), injections of polyinosine-polycytidylic acid (poly I:C) on days -3, -2, and -1 (no-KRV control), and poly I:C treatment followed by injection of KRV (Kilham rat virus) on day 0. For the poly IC+KRV treatment pancreatic islet cells were also extracted on days 7 and 9 post-treatment to observe the onset of insulitis over time. 10X single-cell RNA-Seq was performed on each sample and bioinformatic and imaging analysis was applied to identify the cell type subsets and identify the genes and spatial distribution of cells involved in the onset of autoimmune diabetes.