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

Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types.Methods: Male Apolipoprotein deficient (ApoE−/−) mice at 28 weeks of age were infused...

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Main Authors: Cheng Xu, Xiaowei Liu, Xiaoxin Fang, Lei Yu, Hui Chong Lau, Danlei Li, Xiaoman Liu, Haili Li, Justin Ren, Baohui Xu, Jianjun Jiang, Lijiang Tang, Xiaofeng Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.836593/full
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author Cheng Xu
Xiaowei Liu
Xiaoxin Fang
Lei Yu
Hui Chong Lau
Danlei Li
Xiaoman Liu
Haili Li
Justin Ren
Baohui Xu
Jianjun Jiang
Lijiang Tang
Xiaofeng Chen
Xiaofeng Chen
author_facet Cheng Xu
Xiaowei Liu
Xiaoxin Fang
Lei Yu
Hui Chong Lau
Danlei Li
Xiaoman Liu
Haili Li
Justin Ren
Baohui Xu
Jianjun Jiang
Lijiang Tang
Xiaofeng Chen
Xiaofeng Chen
author_sort Cheng Xu
collection DOAJ
description Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types.Methods: 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.Results: 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.Conclusion: 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.
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spelling doaj.art-690fbef61bcf4b62ae26ec2e6ac2bc772022-12-22T01:42:41ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.836593836593Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic DissectionCheng Xu0Xiaowei Liu1Xiaoxin Fang2Lei Yu3Hui Chong Lau4Danlei Li5Xiaoman Liu6Haili Li7Justin Ren8Baohui Xu9Jianjun Jiang10Lijiang Tang11Xiaofeng Chen12Xiaofeng Chen13Department of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Cardiology, Zhejiang Hospital, Hangzhou, ChinaDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Medicine, Crozer-Chester Medical Center, Upland, PA, United StatesDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Surgery, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Cardiology, Zhejiang Hospital, Hangzhou, ChinaDepartment of Cardiology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, ChinaDepartment of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, United StatesPurpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types.Methods: 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.Results: 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.Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.836593/fullaortic dissectionsingle-cell RNA sequencinggene ontology enrichment analysissmooth muscle cellsKEGG enrichment analysis
spellingShingle Cheng Xu
Xiaowei Liu
Xiaoxin Fang
Lei Yu
Hui Chong Lau
Danlei Li
Xiaoman Liu
Haili Li
Justin Ren
Baohui Xu
Jianjun Jiang
Lijiang Tang
Xiaofeng Chen
Xiaofeng Chen
Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
Frontiers in Genetics
aortic dissection
single-cell RNA sequencing
gene ontology enrichment analysis
smooth muscle cells
KEGG enrichment analysis
title Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
title_full Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
title_fullStr Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
title_full_unstemmed Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
title_short Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
title_sort single cell rna sequencing reveals smooth muscle cells heterogeneity in experimental aortic dissection
topic aortic dissection
single-cell RNA sequencing
gene ontology enrichment analysis
smooth muscle cells
KEGG enrichment analysis
url https://www.frontiersin.org/articles/10.3389/fgene.2022.836593/full
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