Diabetes changes gene expression but not DNA methylation in cardiac cells,Journal of Molecular and Cellular Cardiology

当前位置： X-MOL 学术 › J. Mol. Cell. Cardiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Diabetes changes gene expression but not DNA methylation in cardiac cells
Journal of Molecular and Cellular Cardiology ( IF 4.9 ) Pub Date : 2020-11-14 , DOI: 10.1016/j.yjmcc.2020.11.004
Achim Lother ₁ , Olga Bondareva ₂ , Ali R Saadatmand ₃ , Luisa Pollmeier ₂ , Carmen Härdtner ₄ , Ingo Hilgendorf ₄ , Dieter Weichenhan ₅ , Volker Eckstein ₆ , Christoph Plass ₅ , Christoph Bode ₄ , Johannes Backs ₃ , Lutz Hein ₇ , Ralf Gilsbach ₈

Affiliation

Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Germany; Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Germany.
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Germany.
Institute of Experimental Cardiology, Heidelberg University, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Heidelberg, Germany.
Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Germany.
Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany.
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Germany; Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany; German Centre of Cardiovascular Research (DZHK), partner site RheinMain, Frankfurt am Main, Germany.

Background

Diabetes mellitus is a worldwide epidemic that causes high mortality due to cardiovascular complications, in particular heart failure. Diabetes is associated with profound pathophysiological changes in the heart. The aim of this study was to investigate the impact of diabetes on gene expression and DNA methylation in cardiac cells.

Methods and results

Transcriptome analysis of heart tissue from mice with streptozotocin-induced diabetes revealed only 39 genes regulated, whereas cell type-specific analysis of the diabetic heart was more sensitive and more specific than heart tissue analysis and revealed a total of 3205 differentially regulated genes in five cell types. Whole genome DNA methylation analysis with basepair resolution of distinct cardiac cell types identified highly specific DNA methylation signatures of genic and regulatory regions. Interestingly, despite marked changes in gene expression, DNA methylation remained stable in streptozotocin-induced diabetes. Integrated analysis of cell type-specific gene expression enabled us to assign the particular contribution of single cell types to the pathophysiology of the diabetic heart. Finally, analysis of gene regulation revealed ligand-receptor pairs as potential mediators of heterocellular interaction in the diabetic heart, with fibroblasts and monocytes showing the highest degree of interaction.

Conclusion

In summary, cell type-specific analysis reveals differentially regulated gene programs that are associated with distinct biological processes in diabetes. Interestingly, despite these changes in gene expression, cell type-specific DNA methylation signatures of genic and regulatory regions remain stable in diabetes. Analysis of heterocellular interactions in the diabetic heart suggest that the interplay between fibroblasts and monocytes is of pivotal importance.

中文翻译：

糖尿病改变心脏细胞中的基因表达，但不改变 DNA 甲基化

背景

糖尿病是一种世界范围内的流行病，由于心血管并发症，特别是心力衰竭，导致高死亡率。糖尿病与心脏的深刻病理生理变化有关。本研究的目的是调查糖尿病对心脏细胞基因表达和 DNA 甲基化的影响。

方法和结果

对链脲佐菌素诱导的糖尿病小鼠心脏组织的转录组分析显示，仅 39 个基因受到调节，而糖尿病心脏的细胞类型特异性分析比心脏组织分析更灵敏、更特异，并显示 5 个细胞中总共有 3205 个差异调节基因类型。通过对不同心脏细胞类型的碱基对分辨率进行全基因组 DNA 甲基化分析，确定了基因和调控区域的高度特异性 DNA 甲基化特征。有趣的是，尽管基因表达发生显着变化，但链脲佐菌素诱导的糖尿病中 DNA 甲基化保持稳定。细胞类型特异性基因表达的综合分析使我们能够确定单细胞类型对糖尿病心脏病理生理学的特殊贡献。最后，基因调控分析揭示配体-受体对是糖尿病心脏中异细胞相互作用的潜在介质，其中成纤维细胞和单核细胞显示出最高程度的相互作用。