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

• 作者: Gang Liu Yana Li Tengjiao Zhang Mushan Li Sheng Li Qing He Shuxin Liu Minglu Xu Tinghui Xiao Zhen Shao Weiyang Shi Weida Li
• 来源期刊: 基因组蛋白质组与生物信息学报（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ORIGINAL RESEARCH
• 页码范围: 408-422
• 页数: 15页
• 语种: 英文

摘要

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and patho-genesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D 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 T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.