Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells

Type 2 diabetes(T2 D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2 D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2 D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing(scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2 D mouse model, we identified sex-dependent T2 D altered genes, suggesting sex-based differences in the pathological mechanisms of T2 D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sexmatched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2 D pathogenicity, indicating that sex should be considered when treating T2 D. We hope that our findings could provide new insights for the development of precision medicine in T2 D.