Heterogeneity and characteristic changes in cardiomyocytes and non‑cardiomyocytes following myocardial infarction: Insights from single‑cell sequencing analysis (Review)

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  Figure 1.. Cardiomyocyte cluster typing and marker genes for each cluster. vCM1-vCM5 represent myocardial cell populations under different ventricular conditions, which are determined by characteristics such as stress response, metabolic changes and proliferation. Marker genes such as MYH6 are notably expressed in vCM2, indicating that they are closely related to metabolic activities in myocardial repair. (A) Adult cardiomyocyte cluster typing and marker genes for each cluster. (B) Mouse cardiomyocyte cluster typing and marker genes for each cluster. SnRNA-seq, single-nucleus RNA sequencing; ScRNA-seq, single-cell RNA sequencing; vCM, ventricular cardiomyocyte clusters; aCM, atrial cardiomyocyte clusters; vCM1, functionally maintained cardiomyocytes; vCM2, myocardial cells enriched in the right ventricle (with high expression of MYH6); vCM3, stress-responsive cardiomyocytes (expressing ANKRD1, etc.); vCM4, high-energy metabolic cardiomyocytes (enriched mitochondrial genes, CRYAB); vCM5, electrophysiologically associated cardiomyocytes (high expression of DLC1 and EBF2); aCM1, basic functional cardiomyocytes; aCM2, metabolic regulation of cardiomyocytes in the right atrium (predominantly…

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  Figure 2.. Endothelial cell cluster typing and marker genes for each cluster. The high expression of capillary marker Gpihbp1 in VEC1 and VEC2, as well as the enrichment of macrovascular genes such as Plvap and Vwf in VEC3, indicate that they are related to the maintenance of vascular activity and angiogenesis. Endothelial cells have multiple functions in blood vessels, including vascular stability, blood flow regulation, material exchange and immune response. Following myocardial infarction, endothelial cells have the functions of repair, vascular regeneration and remodeling, as well as coagulation. (A) Endothelial cell clusters of ventricular tissue origin and marker genes. (B) Endothelial cell clusters of TIP origin and marker genes. TIP, cardiac interstitial cell population; ScRNA-seq, single-cell RNA sequencing; VEC1-3, venous endothelial cells (VEC1 highly expresses Gpihbp1, VEC2 cluster highly expresses Cxcl1 and Icam1, VEC3 highly expresses Plvap and Vwf); Art.EC, arterial endothelial cells (enriched with artery-related genes such as Cxcl12); Endo, metabolism-related endothelial cells (specifically expressing metabolic genes such as H19 and Cpe); Pro.EC, proliferative active…

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  Figure 3.. Fibroblast cluster typing and marker genes for each cluster. The high expression of myofibroblast marker genes Acta2, Tagln and Cthrc1 in FB1/B group/Fibro-Myo; enrichment of the differentiation inhibitory gene Dlk1 in FB2; the specific expression of the proliferation gene Mki67 in Pro.FB; the upregulation of matrix homeostasis genes Fbln5 and Bgn in FB4; the significant expression of sclerosis-related genes Comp, Cilp and Angptl7 in CF5/CF6 and the enrichment of osteogenic genes Adamtsl2 and paracrine factor SFRP2 in MFCs. This indicates that they are respectively involved in fibrotic driving, differentiation inhibition, proliferation repair, matrix remodeling and chronic scar hardening. (A*) Fibroblast clusters of cardiac interstitial cell origin and marker genes. (B*) Fibroblast clusters of non-cardiomyocyte origin and marker genes. (C*-E*) Fibroblast clusters of cardiac ventricular tissue origin and marker genes. The CF1-CF4 subsets highly express genes related to the degradation of homeostasis fibroblasts (Hsd11b1, Lpl and Dpt) and ECM; CF5 and CF6 express genes related to the activation of fibroblasts, cartilage development and ossification, including Angptl7, Cilp, Comp,…

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  Figure 4.. Monocyte macrophage clusters typing and marker genes for each cluster. High expression of pro-inflammatory genes Ly6c2, S100a8 and the C1q family (*C1qa/b/c*) in M1/MAC-Mo; enrichment of repair genes Spp1, Cd163 and Mrc1 in M2/MAC-TR; the significant upregulation of anti-fibrotic genes Fabp5 and Gpnmb in Bhlhe41+MΦ; the activation of phagocyte-related gene Folr2 in MAC-Gpnmb; and the co-expression of the cross-lineage genes Col1a1 (fibroblast) and Cdh5 (endothelial) in MAC-Fib/MAC-Endo indicates that they are respectively involved in inflammation initiation, tissue repair, fibrosis inhibition, fragment clearance and lineage plasticity. (A) Monocyte cell clusters of Cardiac ventricular tissue origin and marker genes. (B) Monocyte cell clusters of Cardiac CD45+ leukocytes origin and marker genes. (C) Monocyte cell clusters of non-cardiomyocyte origin and marker genes. (D) Monocyte cell clusters of non-cardiomyocyte (temporary cardiac resident macrophage subset) origin and marker genes. The Ccr2_hi cluster contains subgroups such as MAC_Mo/M1 and IFNIC and enriches pro-inflammatory transcription factors such as Stat1 and Irf7. The Ccr2_lo cluster contains subgroups such as MAC-TR,…

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  Figure 5.. T and B cell clusters typing and marker genes for each cluster [MZ marker genes related literature]. High expression of pro-inflammatory factor IL-1β, chemokine Ccl6 and transcription factor Irf5/Fosb in effector T cells regulate the enrichment of immune regulatory pathways (such as Sp1) in T cells; co-activation of the dual-chemokine receptor Cxcr5/Ccr7 and the tissue repair factor Tgfb1 in hB cells; and upregulation of the cell cycle gene Trp53/Cdc27 in Cyc B cells indicates that they are respectively involved in inflammatory drive, immunosuppression, repair chemotaxis and proliferation responses. (A) T cell clusters typing and marker genes for each cluster. (B) Cell clusters typing and marker genes for each cluster. ScRNA-seq, single-cell RNA sequencing; Naive T cells, immune response preparatory T cells; effector T cells, pro-inflammatory injury type T cells (expressing Ccl6 and IL-1β); regulatory T cells, immunosuppressive T cells (rich in Sp1 regulators); NK cells, direct killer T cells; B1 cells, natural immune barrier type B cells; B2 cells, lymphoid tissue localization type B cells; marginal zone B cells (MZ), rapid antibody-responsive B cells; germinal center B cells…

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  Figure 6.. Major Interactions between cells in the heart following MI. It mainly demonstrates the interactions among cardiomyocytes, macrophages, endothelial cells and fibroblasts in the heart after myocardial infarction and also involves a few epicardial cells. It clearly shows the roles of cardiomyocytes in stress compensation after myocardial infarction, endothelial cells in promoting angiogenesis and regulating inflammation, macrophages in promoting inflammation, angiogenesis and remodeling and fibroblasts in repairing scar formation and promoting fibrosis. OSM, oncostatin M; CM, cardiomyocyte; MMP14/MT1-MMP, membrane-type matrix metalloproteinase-1; METRNL, meteorin-like.