BioProject

Type 1 diabetes (T1D) is characterized by immune mediated destruction of insulin producing β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Aims: Towards the goal of informing T1D biomarker strategies, we profiled different classes of RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ to mimic the pro-inflammatory T1D milieu. Total RNA and small RNA sequencing were performed to identify long (mRNA and long non-coding RNAs) and different classes of small non-coding RNAs. RNAs with fold change ≥ 1.3 and p-value < 0.05 were considered as differentially expressed. mRNAs and miRNAs species represented the most abundant long and small RNA species, respectively. Expression patterns of each class of RNA were changed with cytokine treatment. Differentially expressed long RNAs and targets of small non-coding RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis and apoptosis. Our data provides the first comprehensive catalog of protein coding and non-coding RNAs in human islet-derived exosomes and identifies RNAs that are dysregulated under cytokine stress. Overall design: Identification of differentially expressed mRNA from Brefeldin A treated vs. control human pancreatic islets.