The single-cell RNA sequencing (scRNA-seq) transcriptome profile of pancreatic islets in three types of diabetic mice and its pathological changes

Accurate diabetic mouse models are very necessary for basic and clinical diabetes research. Different induction conditions and genetic changes in mouse diabetes models may lead to different classification and expression of islet cell sub-populations. In this study, we first examined the pathologic phenotypic differences of wild C57BL/6J mice (WT) and three types of diabetic mice: high-fat diet (HFD) fed mice (DIO), db/db mice (T2D) and streptozotocin (STZ) induced mice (T1D). Then we described a complete islet cell landscape and identified robust marker genes for each endocrine cell type by analyzing the gene expression of islet cells in the above three types of diabetic mice using publicly available scRNA-Seq data. We also identified α, β, δ and PP cell sub-populations genes expression profile and KEGG and GO analysis in three diabetic mouse models, and explored their similarities and differences. Furthermore, we classified the β-cell populations of three types of diabetic mice and humans with type 2 diabetes and identified differential genes. Experimental verification was conducted on β-cell differential genes such as Scg2 and G6pc2 between different models. We found Scg2 ^High beta cells may represent in energy-hyperactive diabetes. G6pc2 ^High beta cells showed an enrichment pattern in the HFD group. In summary, our work provides a deeper understanding of the pathogenesis and usage scenarios of three commonly used diabetic mouse models through single-cell sequencing analysis of pancreatic islets.