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

作　　者：王贤德 乔博康 贾立昕[2] 杜杰[2] WANG Xiande;QIAO Bokang;JIA Lixin;DU Jie(School of Basic Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院,100069 [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

出　　处：《心肺血管病杂志》2024年第2期194-200,共7页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(82070407)。

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Ang Ⅱ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,Ang Ⅱ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:Ang Ⅱ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。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 Ang II infusion.Method:Heart tissue from mice was collected before(control group)and one week after micropump 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. Oneweek after Ang II infusion, there was an increased proportion of fibroblast subgroups involved in inflammatoryresponse and regulation of blood vessel formation. Conclusions: Ang II infusion led to an increase in theproportion of fibroblasts and macrophages in cardiac tissue. Among the fibroblasts, subgroups that promoteinflammatory 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 

分 类 号：R54[医药卫生—心血管疾病]