摘要：SummaryCoxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice. Chronically affected mice may develop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells from healthy and myocarditic mice, leading us to note significant proportions of myeloid cells, T cells, and fibroblasts. Although the transcriptomes of myeloid cells were mainly of M2 phenotype, the Th17 cells, CTLs, and Treg cells had signatures critical for cytotoxic functions. Fibroblasts were heterogeneous expressing genes important in fibrosis and regulation of inflammation and immune responses. The intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells had upregulated unique transcription factors modulating cardiac remodeling functions. Together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.Graphical abstractDisplay OmittedHighlights•M2 cells, T cells, and fibroblasts predominated myocarditic hearts•Transcriptomes of Th17 and Treg cells mainly represented signatures of cytotoxicity•Fxyd6andCyb5amay be novel cardiac injury markers of fibroblasts•Ets1andMafbwhich modulate fibrosis-inducing genes may be therapeutic targetsPathophysiology; Systems biology; Transcriptomics
