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

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 sing...

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Autores principales: Liu, Gang, Li, Yana, Zhang, Tengjiao, Li, Mushan, Li, Sheng, He, Qing, Liu, Shuxin, Xu, Minglu, Xiao, Tinghui, Shao, Zhen, Shi, Weiyang, Li, Weida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864195/
https://www.ncbi.nlm.nih.gov/pubmed/34571259
http://dx.doi.org/10.1016/j.gpb.2021.07.004
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author Liu, Gang
Li, Yana
Zhang, Tengjiao
Li, Mushan
Li, Sheng
He, Qing
Liu, Shuxin
Xu, Minglu
Xiao, Tinghui
Shao, Zhen
Shi, Weiyang
Li, Weida
author_facet Liu, Gang
Li, Yana
Zhang, Tengjiao
Li, Mushan
Li, Sheng
He, Qing
Liu, Shuxin
Xu, Minglu
Xiao, Tinghui
Shao, Zhen
Shi, Weiyang
Li, Weida
author_sort Liu, Gang
collection PubMed
description 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.
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spelling pubmed-88641952022-03-02 Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells Liu, Gang Li, Yana Zhang, Tengjiao Li, Mushan Li, Sheng He, Qing Liu, Shuxin Xu, Minglu Xiao, Tinghui Shao, Zhen Shi, Weiyang Li, Weida Genomics Proteomics Bioinformatics Original Research 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. Elsevier 2021-06 2021-09-24 /pmc/articles/PMC8864195/ /pubmed/34571259 http://dx.doi.org/10.1016/j.gpb.2021.07.004 Text en © 2021 Beijing Institute of Genomics https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research
Liu, Gang
Li, Yana
Zhang, Tengjiao
Li, Mushan
Li, Sheng
He, Qing
Liu, Shuxin
Xu, Minglu
Xiao, Tinghui
Shao, Zhen
Shi, Weiyang
Li, Weida
Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title_full Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title_fullStr Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title_full_unstemmed Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title_short Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
title_sort single-cell rna sequencing reveals sexually dimorphic transcriptome and type 2 diabetes genes in mouse islet β cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864195/
https://www.ncbi.nlm.nih.gov/pubmed/34571259
http://dx.doi.org/10.1016/j.gpb.2021.07.004
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