Mouse Single Pancreatic β Cell Transcriptomics Reveal Sexual Dimorphism of Transcriptomes and Identify Sex-dependent Type 2 Diabetes Altered Genes

Published: Sept. 22, 2020, 7:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.22.307421v1?rss=1 Authors: Liu, G., Li, Y., Zhang, T., Li, M., Li, S., Liu, S., Xu, M., Zhen, S., Shi, W., Li, W. Abstract: Type 2 diabetes, characterized by malfunction of pancreatic {beta} cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in mouse {beta} cells. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in high fat diet induced T2D model, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in {beta} cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine. Copy rights belong to original authors. Visit the link for more info