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

Gang Liu; Yana Li; Tengjiao Zhang; Mushan Li; Sheng Li; Qing He; Shuxin Liu; Minglu Xu; Tinghui Xiao; Zhen Shao; Weiyang Shi; Weida Li

doi:10.1016/j.gpb.2021.07.004

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

Genomics Proteomics Bioinformatics. 2021 Jun;19(3):408-422. doi: 10.1016/j.gpb.2021.07.004. Epub 2021 Sep 24.

Authors

Gang Liu¹, Yana Li², Tengjiao Zhang³, Mushan Li⁴, Sheng Li¹, Qing He¹, Shuxin Liu¹, Minglu Xu¹, Tinghui Xiao¹, Zhen Shao⁵, Weiyang Shi⁶, Weida Li⁷

Affiliations

¹ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Tsingtao Advanced Research Institute, Tongji University, Qingdao 266073, China.
² CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
⁴ Department of Statistics, The Pennsylvania State University, University Park, PA 16802, USA.
⁵ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: shaozhen@picb.ac.cn.
⁶ Ministry of Education Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China. Electronic address: wshi@ouc.edu.cn.
⁷ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Tsingtao Advanced Research Institute, Tongji University, Qingdao 266073, China. Electronic address: liweida@tongji.edu.cn.

Abstract

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis 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 of β cells. 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.

Keywords: Pancreatic β cell; Precision medicine; Sex-biased gene expression; Sex-dependent T2D altered genes; Type 2 diabetes mellitus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental* / genetics
Diabetes Mellitus, Experimental* / metabolism
Diabetes Mellitus, Type 2* / pathology
Female
Insulin-Secreting Cells* / metabolism
Insulin-Secreting Cells* / pathology
Male
Mice
Sequence Analysis, RNA
Transcriptome