心肺血管病杂志2024,Vol.43Issue(2) :194-200.DOI:10.3969/j.issn.1007-5062.2024.02.016

利用单细胞测序探讨高血压对小鼠心脏中不同细胞类型改变的影响

Exploring the effects of hypertension on change of cell types in the mouse heart by single cell sequencing

王贤德 乔博康 贾立昕 杜杰
心肺血管病杂志2024,Vol.43Issue(2) :194-200.DOI:10.3969/j.issn.1007-5062.2024.02.016

利用单细胞测序探讨高血压对小鼠心脏中不同细胞类型改变的影响

Exploring the effects of hypertension on change of cell types in the mouse heart by single cell sequencing

王贤德 1乔博康 2贾立昕 2杜杰2
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作者信息

  • 1. 100069 首都医科大学基础医学院
  • 2. 首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所
  • 折叠

摘要

目的:利用单细胞测序技术分析野生C57B/L6小鼠在血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)灌注前后心脏组织中细胞组成,尤其是心脏成纤维细胞亚群改变,旨在探讨AngⅡ灌注引起的高血压心脏重构过程中成纤维细胞的变化特征.方法:收取Ang Ⅱ微量泵灌注前(对照组)及灌注1周后的小鼠心脏组织进行单细胞测序.对测序数据进行质控、标准化、降维、tSNE聚类、细胞类型注释及占比以及随后的功能富集分析.结果:根据心脏组织细胞的特征基因将小鼠心脏组织中细胞分为7群,主要为内皮细胞、成纤维细胞和巨噬细胞.其中,AngⅡ灌注后成纤维细胞(13.7%vs.24.3%)和巨噬细胞(7.7%vs.22.1%)占比增加,内皮细胞占比减少(72.6%vs.47.6%).心脏成纤维细胞可以被分为6个亚群,分别发挥促进细胞外基质形成、细胞黏附及调控血管新生等功能.Ang Ⅱ灌注1周后参与炎症反应和调控血管形成的成纤维细胞亚群占比增加.结论:AngⅡ灌注升高心脏组织中成纤维细胞和巨噬细胞占比增加.其中成纤维细胞主要为促进炎症反应和调控血管生成的亚群.

Abstract

Objective:To analyze the changes in cellular composition in the heart tissue of wild-type C57B/L6 mice before and after Angiotensin Ⅱ(Ang Ⅱ)infusion using single-cell sequencing technology,particularly focusing on the changes in cardiac fibroblast subpopulations,with the aim of investigating the characteristics of fibroblast alterations during the hypertensive cardiac remodeling process induced by AngⅡ infusion.Method:Heart tissue from mice was collected before(control group)and one week after micro-pump infusion of Ang Ⅱ for single-cell sequencing.The sequencing data were subjected to quality control,normalization,dimension reduction,tSNE clustering,cell type annotation and proportion analysis,followed by functional enrichment analysis.Results:Cells in the mouse heart tissue were classified into seven groups based on characteristic genes,primarily endothelial cells,fibroblasts,and macrophages.After Ang Ⅱ infusion,there was an increase in the proportion of fibroblasts(13.7%vs.24.3%)and macrophages(7.7%vs.22.1%),and a decrease in endothelial cells(72.6%vs.47.6%).Cardiac fibroblasts could be divided into six subgroups,each playing roles in promoting extracellular matrix formation,cell adhesion,and regulating angiogenesis.One week after Ang Ⅱ infusion,there was an increased proportion of fibroblast subgroups involved in inflammatory response and regulation of blood vessel formation.Conclusions:Ang Ⅱ infusion led to an increase in the proportion of fibroblasts and macrophages in cardiac tissue.Among the fibroblasts,subgroups that promote inflammatory responses and regulate blood vessel formation were predominant.

关键词

单细胞测序/血管紧张素Ⅱ灌注/小鼠心脏/成纤维细胞

Key words

Single-cell sequencing/Angiotensin Ⅱ infusion/Mouse heart/Fibroblast

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基金项目

国家自然科学基金(82070407)

出版年

2024
心肺血管病杂志
北京市心肺血管疾病研究所,首都医科大学附属北京安贞医院

心肺血管病杂志

CSTPCD
影响因子:1.214
ISSN:1007-5062
参考文献量14
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