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Title:
Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level | Basic Research in Cardiology
Description:
Inflammation and fibrosis are intertwined mechanisms fundamentally involved in heart failure. Detailed deciphering gene expression perturbations and cell–cell interactions of leukocytes and non-myocytes is required to understand cell-type-specific pathology in the failing human myocardium. To this end, we performed single-cell RNA sequencing and single T cell receptor sequencing of 200,615 cells in both human dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) hearts. We sampled both lesion and mild-lesion tissues from each heart to sequentially capture cellular and molecular alterations to different extents of cardiac fibrosis. By which, left (lesion) and right ventricle (mild-lesion) for DCM hearts were harvest while infarcted (lesion) and non-infarcted area (mild-lesion) were dissected from ICM hearts. A novel transcription factor AEBP1 was identified as a crucial cardiac fibrosis regulator in ACTA2+ myofibroblasts. Within fibrotic myocardium, an infiltration of a considerable number of leukocytes was witnessed, especially cytotoxic and exhausted CD8+ T cells and pro-inflammatory CD4+ T cells. Furthermore, a subset of tissue-resident macrophage, CXCL8hiCCR2+HLA-DRhi macrophage was particularly identified in severely fibrotic area, which interacted with activated endothelial cell via DARC, that potentially facilitate leukocyte recruitment and infiltration in human heart failure.
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pubmed, article, google, scholar, cas, central, heart, wang, failure, singlecell, human, cells, chen, zhang, cell, cardiac, nat, httpsdoiorgs, fibrosis, nature, beijing, supplementary, guo, med, china, inflammation, endothelial, myocardial, transcriptional, file, data, research, cellular, factor, macrophage, res, macrophages, circulation, immunol, reveals, university, xlsx, privacy, cookies, content, information, basic, rao, sequencing, inflammatory,
Topics {✒️}
single-cell rna-seq reveals understand cell-type-specific pathology month download article/chapter proinflammatory regulatory t-lymphocytes angiotensin ii-induced expression chronic heart failure tumor necrosis factor-alpha early maternal-fetal interface sls-qidong innovation fund t-cell-mediated lysis article basic research cxcl8hiccr2+hla-drhi macrophage single-cell immune landscape human tissue-resident memory adverse cardiac remodeling cxcl8/il-8 chemokine family full article pdf single-cell sequencing cell receptor sequencing tissue resident ccr2 transcription factor aebp1 single-cell level human dilated cardiomyopathy disease lesions identifies human heart failure resident endothelial cells single-cell analysis article rao jiangping song single-cell reconstruction privacy choices/manage cookies tissue-resident macrophage severe heart failure congestive heart failure nonischemic heart failure keren-shaul adult human heart vascular endothelial cells shengshou hu potentiating cardiomyocyte proliferation biopic facs facility cell–cell interactions pro-inflammatory cd4+ reduces remodeling target gene tlr4 related subjects unique microglia type adaptive partitioning inference activated endothelial cell human atherosclerotic plaques
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