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

糖尿病（Diabetes mellitus, DM）是一类以血糖水平升高为特征的慢性疾病，其发病与功能性β细胞团丢失密切相关。本研究旨在探究人类胰腺细胞对β细胞功能障碍相关病理生理状态的应答反应，最终明确参与糖尿病发生发展的分子机制。本研究将3名非糖尿病供者来源的分离原代人类胰岛体外暴露于促炎、氧化、代谢及内质网应激环境，处理时长最长达3天。随后对细胞进行单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）。对该数据集的分析揭示了各胰腺细胞类型对各类应激条件的共有及特异性分子应答模式。实验整体设计如下：取自非糖尿病供者的胰腺胰岛细胞分别接受以下应激因素处理：葡萄糖（22 mM）和/或棕榈酸（0.5 mM）、毒胡萝卜素（0.1 μM）、白细胞介素1β（1 ng/ml）和/或干扰素γ（1000 U/ml）、干扰素α（2000 U/ml）、过氧化氢（H₂O₂，50 μM）、成纤维细胞生长因子2（100 ng/ml）及低氧环境，同时设置未处理组作为对照，处理时长分别为24小时与72小时。