Elgamal Ruth M, Kudtarkar Parul, Melton Rebecca L, Mummey Hannah M, Benaglio Paola, Okino Mei-Lin, Gaulton Kyle J
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA.
Department of Pediatrics, University of California, San Diego, La Jolla, CA.
Diabetes. 2023 Nov 1;72(11):1719-1728. doi: 10.2337/db23-0130.
Pancreatic islets consist of multiple cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in type 1 and type 2 diabetes. Numerous studies have assessed transcription across individual cell types using single-cell assays; however, there is no canonical reference of gene expression in islet cell types that is also easily accessible for researchers to query and use in bioinformatics pipelines. Here we present an integrated map of islet cell type-specific gene expression from 192,203 cells from single-cell RNA sequencing of 65 donors without diabetes, donors who were type 1 diabetes autoantibody positive, donors with type 1 diabetes, and donors with type 2 diabetes from the Human Pancreas Analysis Program. We identified 10 distinct cell types, annotated subpopulations of several cell types, and defined cell type-specific marker genes. We tested differential expression within each cell type across disease states and identified 1,701 genes with significant changes in expression, with most changes observed in β-cells from donors with type 1 diabetes. To facilitate user interaction, we provide several single-cell visualization and reference mapping tools, as well as the open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology.
胰岛由多种细胞类型组成，这些细胞会产生维持葡萄糖稳态所需的激素，而胰岛功能障碍是1型和2型糖尿病的主要因素。许多研究已经使用单细胞分析方法评估了单个细胞类型的转录情况；然而，目前还没有一个规范的胰岛细胞类型基因表达参考图谱，供研究人员在生物信息学流程中方便地查询和使用。在此，我们展示了来自人类胰腺分析项目的65名无糖尿病供体、1型糖尿病自身抗体阳性供体、1型糖尿病供体和2型糖尿病供体的192,203个单细胞RNA测序数据所构建的胰岛细胞类型特异性基因表达综合图谱。我们鉴定出了10种不同的细胞类型，对几种细胞类型的亚群进行了注释，并定义了细胞类型特异性标记基因。我们测试了每种细胞类型在不同疾病状态下的差异表达，确定了1701个表达有显著变化的基因，其中大部分变化出现在1型糖尿病供体的β细胞中。为了便于用户交互，我们提供了几种单细胞可视化和参考图谱工具，以及用于创建此参考图谱的开放获取分析流程。这些结果将为研究胰岛生物学的研究人员提供宝贵的资源。
