Single-cell transcriptomics of primary human pancreatic islet cells exposed to stress conditions associated with beta-cell failure.

Diabetes mellitus (DM) is a chronic disease associated with elevated blood glucose level and resulting from a loss of functional beta-cell mass. The goal of this study is to investigate the response of human pancreatic cells to pathophysiological conditions associated with beta-cell dysfunction, ultimately to identify molecular mechanisms contributing to the development of diabetes. Isolated primary human islets from three non-diabetic donors were exposed in vitro to pro-inflammatory, oxidative, metabolic and endoplasmic reticulum stress for up to 3 days. Subsequently the cells were processed for single-cell RNA sequencing (scRNA-seq). Analysis of the dataset revealed both common and specific molecular response of each pancreatic cell type to the various stress conditions. Pancreatic islet cells from non-diabetic donors were treated with stressors (glucose (22 mM) and/or palmitate (0.5 mM), thapsigargin (0.1 μM), IL-1β (1 ng/ml) and/or IFNγ (1000 U/ml), IFNα (2000 U/ml), hydrogen peroxide (H2O2, 50 μM), FGF2 (100 ng/ml), hypoxia) and untreated as control for 24h and 72h