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Title:
Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm | Cell Communication and Signaling
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Background and objectives Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Methods Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package âSeuratâ. Cell annotation was determined by the R package âsingleRâ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cellâcell junctions and cellâmatrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package âMonocle2â. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. Results A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. Conclusion A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process. Video Abstract
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vsmcs, aortic, pubmed, cells, article, fig, cell, aneurysm, google, scholar, macrophagelike, phenotypes, expression, cas, vascular, muscle, analysis, smooth, contractile, aorta, central, genes, normal, tcelllike, mesenchymallike, markers, fibroblastlike, data, phenotypic, levels, phenotype, communication, singlecell, cellcell, gene, ecm, rna, adipocytelike, high, collagen, aneurysms, junction, present, acta, res, study, cellmatrix, matrix, abdominal, vsmc,
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predominant rhoa/rock-dependent mechanism single-cell genomics reveals single-cell transcriptome cellâcell junction score cellâcell junction scores cell junction-related pathways cellâmatrix junction score cellâmatrix junction scores single-cell trajectory analysis natural scientific research project strong cellâmatrix adhesion incoming/outgoing communication patterns full size image article download pdf cellâcell communication analysis integrin-based focal adhesions network central plot full-thickness aortic aneurysms vsmcs-derived intermediate cell lipid-rich necrotic cores mfg-e8 activates proliferation reduced cellâmatrix adhesion single-cell data smooth muscle cells ďż˝smooth muscle cellsâ smooth-muscle cells aortic aneurysm-derived vsmcs specifically regulated t-cell vascular diseases ligandâreceptor pairs mif mif signalling-mediated network phenotype-based trajectory plot cellâcell adhesion klf4-dependent phenotypic modulation cellâmatrix scores cellâcell junctions lineage-tracing techniques cellâcell communication cell-cell communication cellâmatrix junctions gene expression log-normalized randomized controlled trial normal aorta-derived vsmcs cellâcell communications privacy choices/manage cookies reference-based analysis stem cell markers significant signalling pathways form numerous myofilaments sufficient focal adhesions
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headline:Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm
description:Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package âSeuratâ. Cell annotation was determined by the R package âsingleRâ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cellâcell junctions and cellâmatrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package âMonocle2â. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process.
datePublished:2023-05-15T00:00:00Z
dateModified:2023-05-15T00:00:00Z
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license:http://creativecommons.org/publicdomain/zero/1.0/
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keywords:
Vascular smooth muscle cells
Phenotypes
Single-cell transcriptome analysis
Aortic aneurysm
Cell Biology
Protein-Ligand Interactions
Receptors
Cytokines and Growth Factors
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headline:Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm
description:Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package âSeuratâ. Cell annotation was determined by the R package âsingleRâ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cellâcell junctions and cellâmatrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package âMonocle2â. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process.
datePublished:2023-05-15T00:00:00Z
dateModified:2023-05-15T00:00:00Z
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Vascular smooth muscle cells
Phenotypes
Single-cell transcriptome analysis
Aortic aneurysm
Cell Biology
Protein-Ligand Interactions
Receptors
Cytokines and Growth Factors
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