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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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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. |
format | Online Article Text |
id | pubmed-8864195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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