Single-cell RNA-sequencing reveals profound changes in circulating immune cells in patients with heart failure
Single-cell RNA-sequencing reveals profound changes in circulating immune cells in patients with heart failure
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DOI：
10.1093/cvr/cvaa101
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发表时间：
2021-02-01
影响因子：
10.8
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
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作者：
Abplanalp, Wesley T.;John, David;Dimmeler, Stefanie
在单细胞水平上识别免疫细胞的特征可能为免疫相关疾病的变化提供新的见解。因此，我们使用单细胞RNA测序，以确定心力衰竭对循环免疫cells.Methods和结果的影响，我们证明了一个显着的变化，单核细胞与T细胞的比例在心力衰竭患者，与健康受试者相比，这是通过流式细胞术分析验证。单核细胞的亚群和根据相对CD 14和FCGR 3A（CD 16）表达的簇的分层允许经典、中间和非经典单核细胞的注释。心力衰竭对这些亚群的基因表达模式有特定的影响。代谢活性基因如FABP 5在心力衰竭患者的经典单核细胞中高度富集，而β-连环蛋白表达在中间单核细胞中显著更高。经典和多因素降维流式细胞术analysis.Conclusion这项研究表明，来自心力衰竭患者的循环细胞有改变的表型的选择性调节的签名在单核细胞亚群进行了验证。与健康受试者相比，这些数据为识别心力衰竭中免疫细胞的特征提供了丰富的来源。所观察到的FABP 5和Wnt信号传导特征的增加可能有助于增强单核细胞活化。[图形]。
Aims Identification of signatures of immune cells at single-cell level may provide novel insights into changes of immune-related disorders. Therefore, we used single-cell RNA-sequencing to determine the impact of heart failure on circulating immune cells.Methods and results We demonstrate a significant change in monocyte to T-cell ratio in patients with heart failure, compared to healthy subjects, which were validated by flow cytometry analysis. Subclustering of monocytes and stratification of the clusters according to relative CD14 and FCGR3A (CD16) expression allowed annotation of classical, intermediate, and non-classical monocytes. Heart failure had a specific impact on the gene expression patterns in these subpopulations. Metabolically active genes such as FABP5 were highly enriched in classical monocytes of heart failure patients, whereas beta-catenin expression was significantly higher in intermediate monocytes. The selective regulation of signatures in the monocyte subpopulations was validated by classical and multifactor dimensionality reduction flow cytometry analyses.Conclusion Together this study shows that circulating cells derived from patients with heart failure have altered phenotypes. These data provide a rich source for identification of signatures of immune cells in heart failure compared to healthy subjects. The observed increase in FABP5 and signatures of Wnt signalling may contribute to enhanced monocyte activation.[GRAPHICS].