High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis [scRNA-seq]
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PROVIDER: PRJNA1067646 | ENA |
REPOSITORIES: ENA
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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:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis
| PRJNA1067637 | ENA
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:High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis [CITE-seq]
| PRJNA1067645 | ENA
Project description:Cardiovascular diseases represent a leading cause of deaths globally; of which atherosclerosis is a major contributor. Selective retention of circulating apolipoprotein B particles in the sub endothelial space by arterial wall proteoglycans and their subsequent modification is currently thought to be a hallmark of the disease. The exact mechanism responsible for lesion development is not fully understood. Currently, ultrasonic assessment of carotid artery intima media thickness (IMT) is commonly used as a pre-clinical marker of atherosclerosis. However, as the onset of atherosclerotic process and the appearance of carotid artery plaque can vary, the identification of additional biomarkers showing potential etiological aspects of disease is an important goal. This study describes the use of a label free mass spectrometry approach in the proteomics analysis of serum samples from control and atherosclerotic subjects. The samples were from a study cohort recruited in The Cardiovascular Risk in Young Finns Study, with a goal of identifying biomarkers for atherosclerosis. Samples from 43 individuals with a early non-obstructive plaques and 43 controls were used (Matched by age, sex, body size and systolic blood pressure).
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Project description:Atherosclerotic plaques belong to the common vascular disease in the aged, which rupture will lead to acute thromboembolic diseases, the major reason for fatal cardiovascular events. Accumulating evidence indicates that lncRNAs exert critical functions in atherosclerosis. To identify novel astherosclerotic plaques-relevant lncRNAs, four specimens of carotid atherosclerotic plaque were collected, and endovascular tissue one centimeter far from the carotid atherosclerotic plaque was taken as a control group, we performed lncRNA microarray analysis using Affymetrix Human OElncRNA
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2024-04-12 | GSE253904 | GEO
Project description:Atherosclerosis (AS) is the underlying pathological process of severe cardiovascular or cerebrovascular diseases, whereas the molecular and cellular complexity of AS remains poorly elucidated. We here compared the expression of mRNA, lncRNA, circRNA in peripheral white blood cells (PWBCs) from carotid atherosclerotic plaque (CAP)-positive patients and CAP-negative controls through mRNA, lncRNA, and circRNA microarrays. A total of 552 mRNAs, 1,296 lncRNAs and 667 circRNAs were altered in the pathogenesis of AS.
2023-12-30 | GSE152777 | GEO
Project description:NOVEL FACTORS FOR UNEXPLAINED PHENOTYPES OF SUBCLINICAL CAROTID ATHEROSCLEROSIS
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