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      Heterogeneity of immune cells in human atherosclerosis revealed by scRNA-Seq

      1 , 2 , 3 , 2 , 1 , 4
      Cardiovascular Research
      Oxford University Press (OUP)

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          Abstract

          Immune cells in atherosclerosis include T, B, natural killer (NK) and NKT cells, macrophages, monocytes, dendritic cells (DCs), neutrophils, and mast cells. Advances in single-cell RNA sequencing (sRNA-Seq) have refined our understanding of immune cell subsets. Four recent studies have used scRNA-Seq of immune cells in human atherosclerotic lesions and peripheral blood mononuclear cells (PBMCs), some including cell surface phenotypes revealed by oligonucleotide-tagged antibodies, which confirmed known and identified new immune cell subsets and identified genes significantly up-regulated in PBMCs from HIV+ subjects with atherosclerosis compared to PBMCs from matched HIV+ subjects without atherosclerosis. The ability of scRNA-Seq to identify cell types is greatly augmented by adding cell surface phenotype using antibody sequencing. In this review, we summarize the latest data obtained by scRNA-Seq on plaques and human PBMCs in human subjects with atherosclerosis.

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          Most cited references51

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          Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

          Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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            We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.
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              Molecular and cellular insights into T cell exhaustion.

              In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.
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                Author and article information

                Contributors
                Journal
                Cardiovascular Research
                Oxford University Press (OUP)
                0008-6363
                1755-3245
                August 03 2021
                August 03 2021
                Affiliations
                [1 ]Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA, USA
                [2 ]Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
                [3 ]Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
                [4 ]Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
                Article
                10.1093/cvr/cvab260
                34343272
                e6679a65-52ac-421d-baa8-56ae3d786edc
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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