Key Cell Types and Biomarkers in Heart Failure Identified through Analysis of Single-Cell and Bulk RNA Sequencing Data

IF 4.4 3区 医学 Q2 CELL BIOLOGY
Ying Kong, Ning Yang, Zhiqing Luo, Ruiting Huang, Quhuan Li
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引用次数: 0

Abstract

Heart failure (HF) is a complex clinical syndrome resulting from various cardiac diseases and a significant medical issue worldwide. Although the role of inflammation in HF pathogenesis is well-known, the specific cell types and regulatory molecules involved remain poorly understood. Here, we identified key cell types and novel biomarkers via an analysis of single-cell and bulk RNA sequencing data obtained from patients with two major HF types of ischemic cardiomyopathy and dilated cardiomyopathy. Myeloid cells were identified as the primary cell population involved in HF through cellular fraction and gene set enrichment analysis. Additionally, differential analysis of myeloid cells revealed crosstalk between cellular communication and cytokine-regulated immune responses in HF, with the MIF pathway emerging as a crucial immune regulatory pathway. The CD74/CXCR4 receptor complex in myeloid cell subgroup Mφ2 was significantly upregulated, potentially acting as a crucial regulator in HF. Upon receiving the MIF signal molecule, the CD74/CXCR4 receptor can activate NF-κB signaling to produce chemokines and thereby enhance the inflammatory response. CD74 and CXCR4 may serve as biomarkers and treatment targets for HF.
通过分析单细胞和大容量 RNA 测序数据确定心力衰竭的关键细胞类型和生物标志物
心力衰竭(HF)是由多种心脏疾病引起的一种复杂的临床综合征,也是世界范围内的一个重要医学问题。尽管炎症在心力衰竭发病机制中的作用众所周知,但人们对其中涉及的特定细胞类型和调控分子仍然知之甚少。在这里,我们通过分析从缺血性心肌病和扩张型心肌病这两种主要高房颤动类型患者身上获得的单细胞和大量 RNA 测序数据,确定了关键细胞类型和新型生物标记物。通过细胞组分和基因组富集分析,确定髓系细胞是参与心房颤动的主要细胞群。此外,对髓系细胞的差异分析显示了高频心肌病中细胞通讯与细胞因子调控的免疫反应之间的相互影响,其中 MIF 通路是一个关键的免疫调节通路。髓系细胞亚群Mφ2中的CD74/CXCR4受体复合物明显上调,有可能成为高血脂的关键调节因子。在接收到 MIF 信号分子后,CD74/CXCR4 受体可激活 NF-κB 信号,产生趋化因子,从而增强炎症反应。CD74 和 CXCR4 可作为高血压的生物标志物和治疗靶点。
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来源期刊
Mediators of Inflammation
Mediators of Inflammation 医学-免疫学
CiteScore
8.70
自引率
0.00%
发文量
202
审稿时长
4 months
期刊介绍: Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
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