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bioRxiv · 10.1101/2020.09.22.307421

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

Liu, G.·Li, Y.·Zhang, T.·Li, M.·Li, S.·Liu, S.·Xu, M.·Zhen, S.·Shi, W.·Li, W.
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Abstract

Type 2 diabetes (T2D), 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.

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Liu, G., Li, Y., Zhang, T., Li, M., Li, S., Liu, S., Xu, M., Zhen, S., Shi, W., Li, W.. 2020-09-22. Mouse Single Pancreatic β Cell Transcriptomics Reveal Sexual Dimorphism of Transcriptomes and Identify Sex-dependent Type 2 Diabetes Altered Genes. https://doi.org/10.1101/2020.09.22.307421

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