Macrophage extracellular traps originated from the vascular smooth muscle cells play key roles in atherosclerosis progression [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197073 | GEO | 2022/11/04
REPOSITORIES: GEO
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Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC transdifferentiation into macrophage-like SMCs. Furthermore, during transdifferentiation, the SMCs' expression of PADI4 upregulating and SMC generated extracellular trap, a web-like structure, which plays key role in the development of atherosclerosis plaque. To reveal the potential mechanism of the SMC derived macrophages generated ETs surducing surrounding SMCs within the media of artery during the process of atherosclerosis plaque development, we utilized the dsDNA and H3CIT protein to stimuli the SMCs, the SMC stimulated with 0.2%BSA as coontrol group, we collect the cells and did RNA-sequencing between two groups to find the potential signaling pathway participating in the process
2022-11-04 | GSE197074 | GEO
Project description:The development of atherosclerosis, a chronic disease characterized by the buildup of plaque in arterial walls, involves the contribution of vascular smooth muscle cells (SMCs) and SMC-derived cells. To better understand the specific role of SMCs in atherosclerosis, a transgenic mouse line expressing EGFP-tagged ribosomal protein L10a (EGFP-L10a) under the SMC-specific αSMA promoter (SMCTRAP mice) was developed, enabling translating ribosome affinity purification followed by sequencing (TRAP-Seq). SMCTRAP mice were crossed with an atherosclerosis model (SMCTRAP-Athero mice). Using TRAP-Seq and bulk RNA-Seq, the aortas of 15-month-old SMCTRAP and SMCTRAP-Athero mice were analyzed to identify atherosclerosis-induced changes in the profiles of SMC ribosome-associated RNA. The results showed high enrichment of known SMC-specific genes in the TRAP fraction, indicating the specificity of the construct. The intersection of SMC-specific genes identified by TRAP-Seq, and atherosclerosis-induced genes identified by bulk RNA-Seq revealed the contribution of SMCs to the expression of several known disease-induced genes, as well as the identification of previously unlinked genes in atherosclerosis that warrant further investigation. These findings provide new insights into the role of SMCs in atherosclerosis and may offer potential targets for future treatments of this chronic disease.
2024-02-08 | GSE225424 | GEO
Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to pathophysiology of atherosclerosis remains elusive. To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques.
2020-10-06 | GSE155513 | GEO
Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to pathophysiology of atherosclerosis remains elusive. To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques.
2020-10-06 | GSE155512 | GEO
Project description:Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypical landscape of the cells within these lesions is limited. To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. We identified 25 cell populations, each with a unique multi-omic signature, including macrophages, T cells, NK cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL1B or C1Q expression, 2 TREM2 positive foam cells (one expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing CITE-seq data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic vs asymptomatic patients. Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types as well as the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.
2024-04-12 | GSE253903 | GEO
Project description:Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypical landscape of the cells within these lesions is limited. To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. We identified 25 cell populations, each with a unique multi-omic signature, including macrophages, T cells, NK cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL1B or C1Q expression, 2 TREM2 positive foam cells (one expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing CITE-seq data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic vs asymptomatic patients. Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types as well as the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.
2024-04-12 | GSE253902 | GEO
Project description:Purpose: The goals of this study are to investigate the effect of miR-21 knockout in aortic smooth muscle cell transcriptome profiling (RNA-seq) to understand how miR-21 regulates SMC plasticity during atherosclerosis. Methods: Aortic smooth muscle cell (SMC) mRNA profiles of 30-week-old wild-type (WT) and SMC specific miR-21 knockout (miR-21fl/flmTmG/Myh11ERT2) mice fed on western diet for 20 weeks were generated by deep sequencing, in triplicate. The sequence reads that passed quality filters were analyzed at the transcript isoform level . qRT–PCR validation was performed using TaqMan and SYBR Green assays to confirm miR-21 knockout. Results: Using an optimized data analysis workflow, we mapped about 60 million sequence reads per sample to the mouse genome (build mm10) and identified 22,836 transcripts in the SMCs of WT and miR-21fl/flmTmG/Myh11ERT2 mice. RNA-seq data revealed ~300 genes differentially expressed in miR-21 knockout SMCs after atherosclerosis. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized pathways that may contribute to SMC function during atherosclerosis progression. Conclusions: Our study represents the first detailed analysis of SMC lacking of miR-21 transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
2022-06-10 | GSE183829 | GEO
Project description:This study compared gene expression in smooth muscle cells (SMCs) in atherosclerosis-prone and atherosclerosis-resistant aorta segments in 4 months old apolipoprotein E-deficient (apoE-/-) mice before plaque development. In a parallel experiment, both regions were compared in young C57Bl/6 mice. Aortas of 3 male and 3 female ApoE-/- mice were isolated, perfused with triton X-100 to remove endothelial cells and divided in an atherosclerosis-prone region (AA: ascending aorta, aortic arch and proximal 2 mm of thoracic aorta) and a resistant region (TA: central thoracic aorta, i.e. 6 mm distal from the proximal 2 mm). Microarray analysis (VIB-MAF) of pooled total RNA showed differential expression (>2-fold difference) for 244 genes. Up- or downregulation in the AA was observed for 186 and 58 genes respectively. Differential expression of 6 genes was confirmed using real-time PCR. The 201 genes that showed exclusively differential expression in apoE-/- mice were related to processes involved in atherosclerosis, such as cell adhesion, proliferation, differentiation, motility and death, lipid metabolism and immune responses. Furthermore, the transcription profile of the AA was in accordance with a more synthetic SMC phenotype. These results point to an altered transcriptome in SMCs in the aorta of apoE-/- mice at the atherosclerosis-prone location before actual lesion development. This suggests that SMCs, in addition to endothelial cells, can facilitate plaque formation at predilection sites. Experiment Overall Design: samples were hyrbidized in dye-swap.
2009-05-27 | E-GEOD-13836 | biostudies-arrayexpress
Project description:While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remain poorly understood. Single cell RNA sequencing (scRNAseq) data generated with SmartSeq2 (~8000 genes/cell) in nearly 19,000 single cells isolated during atherosclerosis progression in mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease (CAD) patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study.Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by three smooth-muscle cells (SMC), and three macrophage (MP) subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type pro-inflammatory/Trem2-high lipid-associated (MP) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of three arterial wall GRNs: GRN33 (MP), GRN39 (SMC) and GRN122(MP) with major contributions to CAD heritability and strong associations with clinical scores of coronary atherosclerosis severity (SYNTAX/Duke scores). The presence and pathophysiological relevance of GRN39 was verified in five independent RNAseq datasets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM, in cultured human vascular SMCs.By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a CAD framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced-stage, symptomatic atherosclerosis.
2024-03-05 | GSE260656 | GEO
Project description:While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remain poorly understood. Single cell RNA sequencing (scRNAseq) data generated with SmartSeq2 (~8000 genes/cell) in nearly 19,000 single cells isolated during atherosclerosis progression in mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease (CAD) patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study.Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by three smooth-muscle cells (SMC), and three macrophage (MP) subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type pro-inflammatory/Trem2-high lipid-associated (MP) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of three arterial wall GRNs: GRN33 (MP), GRN39 (SMC) and GRN122(MP) with major contributions to CAD heritability and strong associations with clinical scores of coronary atherosclerosis severity (SYNTAX/Duke scores). The presence and pathophysiological relevance of GRN39 was verified in five independent RNAseq datasets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM, in cultured human vascular SMCs.By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a CAD framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced-stage, symptomatic atherosclerosis.
2024-03-05 | GSE260657 | GEO