Background: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.
Methods: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing 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.
Results: We identified 25 cell populations, each with a unique multiomic signature, including macrophages, T cells, NK (natural killer) 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 IL-1B (interleukin-1B) or C1Q expression, 2 TREM2-positive foam cells (1 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 cellular indexing of transcriptomes and epitopes by sequencing 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 versus asymptomatic patients.
Conclusions: 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 and the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.
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http://dx.doi.org/10.1161/ATVBAHA.123.320524 | DOI Listing |
Cancer Cell Int
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Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Taiwan.
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Institue of Public Health & Social Sciences(IPH&SS), Khyber Medical University(KMU), Peshawar, Pakistan.
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December 2024
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:
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Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. The present work aimed to explore the function of regulator of Calcineurin 2 (RCAN2) in NAFLD and its related mechanisms. Mice were fed with high-fat diet (HFD) to construct NAFLD model.
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Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:
Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression.
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