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单细胞RNA测序揭示实验性主动脉夹层中平滑肌细胞的异质性。

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection.

作者信息

Xu Cheng, Liu Xiaowei, Fang Xiaoxin, Yu Lei, Lau Hui Chong, Li Danlei, Liu Xiaoman, Li Haili, Ren Justin, Xu Baohui, Jiang Jianjun, Tang Lijiang, Chen Xiaofeng

机构信息

Department of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China.

Department of Cardiology, Zhejiang Hospital, Hangzhou, China.

出版信息

Front Genet. 2022 Aug 11;13:836593. doi: 10.3389/fgene.2022.836593. eCollection 2022.

Abstract

This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the SMCs and functions among various cell types. Male Apolipoprotein deficient (ApoE) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted. AD was successfully induced in ApoE mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis. scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.

摘要

本研究旨在阐明实验性主动脉夹层(AD)主动脉中的细胞图谱,并详细阐述各种细胞类型中的平滑肌细胞(SMCs)及其功能。对28周龄的雄性载脂蛋白缺陷(ApoE)小鼠输注血管紧张素II(2500 ng/kg/分钟)以诱导AD。7天后,采集安乐死小鼠的主动脉用于10×基因组学单细胞RNA测序(scRNA-seq),随后鉴定细胞类型和差异表达基因(DEGs)。进行了基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)分析。ApoE小鼠成功诱导出AD。scRNA-seq鉴定出15个细胞簇和9种细胞类型,包括非免疫细胞(内皮细胞、成纤维细胞和平滑肌细胞)和免疫细胞(B细胞、自然杀伤T细胞、巨噬细胞、树突状细胞、中性粒细胞和肥大细胞)。平滑肌细胞的相对数量发生了显著变化,并且在平滑肌细胞中鉴定出7个核心DEGs(ACTA2、IL6、CTGF、BGN、ITGA8、THBS1和CDH5)。此外,通过单细胞轨迹分析,我们发现平滑肌细胞可分化为8种不同亚型。scRNA-seq技术能够成功鉴定实验性AD中独特的细胞组成。据我们所知,这是第一项提供小鼠AD组织完整细胞图谱的研究,鉴定出了7个核心DEGs和8种平滑肌细胞亚型,并且平滑肌细胞已从基质型演变为炎症型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f237/9403608/6bc49b7efe67/fgene-13-836593-g001.jpg

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