Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories toward type 2 diabetes

To gain insight into the history of islet cell deterioration along the progression from normal glycemic regulation to T2D, we collected surgical pancreatic tissue samples from 133 metabolically phenotyped pancreatectomized patients (PPP). Gene expression profiles of islets isolated by laser capture microdissection (LCM) from resected and snap-frozen pancreas samples were assessed by RNA sequencing. This study includes RNA-Seq samples from pancreatic islets of 133 human donors, stratified into four groups based on their diabetes status: 18 were non-diabetic (ND), 41 had impaired glucose tolerance (IGT), 35 had Type 3c diabetes (T3cD), and 39 had Type 2 diabetes (T2D). The group assignments are based on thresholds defined in the guidelines of the American Diabetes Association. For data analysis, a subset of 92 pancreatic islet samples was defined, which included only those samples in which the gene INS showed the highest expression (i.e., highest normalized counts value). Statistical analyses were performed both on the complete transcriptomics data set and on this restricted data set.

为阐明从血糖稳态调控进展至2型糖尿病（Type 2 diabetes, T2D）过程中胰岛细胞衰退的动态轨迹，我们收集了133例经代谢表型分型的胰腺切除术患者（PPP）的手术胰腺组织样本。本研究通过RNA测序（RNA-seq），对从切除并速冻的胰腺样本中经激光捕获显微切割（laser capture microdissection, LCM）分离得到的胰岛的基因表达谱进行了定量检测。本研究涵盖133名人类供体胰岛的RNA测序样本，依据受试者的糖尿病状态分为四组：18名为非糖尿病者（non-diabetic, ND）、41名糖耐量受损者（impaired glucose tolerance, IGT）、35名3c型糖尿病患者（Type 3c diabetes, T3cD）以及39名2型糖尿病患者（Type 2 diabetes, T2D）。分组标准参照美国糖尿病协会（American Diabetes Association, ADA）指南中设定的阈值制定。在数据分析阶段，我们划定了包含92份胰岛样本的子集，该子集仅纳入胰岛素基因（INS）表达量最高（即标准化计数峰值）的样本。研究分别对完整转录组数据集与该受限数据集开展了统计分析。