RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes

• Published in: Cell metabolism Vol. 24; no. 4; pp. 608 - 615
• Main Authors: Xin, Yurong, Kim, Jinrang, Okamoto, Haruka, Ni, Min, Wei, Yi, Adler, Christina, Murphy, Andrew J., Yancopoulos, George D., Lin, Calvin, Gromada, Jesper
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.10.2016
• Subjects: Animals; Diabetes Mellitus, Type 2 - genetics; Gene Expression Profiling; glucagon; Humans; insulin; Mice; pancreatic islet cell; pancreatic polypeptide; Sequence Analysis, RNA - methods; Signal Transduction - genetics; Single-Cell Analysis - methods; single-cell RNA sequencing; somatostatin; Transcriptome - genetics; type 2 diabetes; single-cell RNA sequencing; type 2 diabetes; insulin; pancreatic islet cell; somatostatin; glucagon; pancreatic polypeptide
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2016.08.018

Pancreatic islet cells are critical for maintaining normal blood glucose levels, and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic α, β, δ, and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell-type-specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human α and β cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community. [Display omitted] •Single-cell RNA sequencing reveals human islet cell-type-specific genes•Type 2 diabetes affects expression of 245 genes•Most of the affected genes have no prior association with islet cell function or growth•Human and mouse islet cell transcriptomes show important differences Xin et al. perform RNA sequencing of single human islet cells from non-diabetic and T2D donors and identify 245 disease-associated genes, the majority of which have no known association with islet function or growth. Comparison of islet cell transcriptomes between mice and humans reveals important species differences in gene expression.