STOmics technology:BGI Stereomics Stereo-Seq

Data type:Spatial transcriptomics

Sample scope:Multiisolate

Summary:Fulminant myocarditis (FM), a severe myocardial inflammatory disease, frequently leads to sudden death in young individuals. This study presents a comprehensive transcriptome analysis of coxsackievirus B3 (CVB3)-induced myocarditis in A/J mice, both pre- and post-treatment, utilizing single-cell and spatial transcriptomics at seven distinct time points. Our research uncovers the pivotal role of mesothelial cells in the pathogenesis of myocarditis, serving as the initial targets for CVB3 that subsequently activate macrophages, fostering an inflammatory environment. This activation cascade leads to the enrichment of macrophages and T cells in the affected myocardial regions, where they contribute to tissue damage through the development of pro-inflammatory 'Inflammatory_Mac' from peripheral monocytes. Moreover, our findings highlight the detrimental impact of Cd8+ effector T cells, which, upon releasing cytotoxic molecules, especially IFN-γ, modulate the expression of Spi1, driving cardiomyocyte death and further exacerbating the disease's progression. Targeting both IFN-γ and Spi1 yield positive treatment effects on FM mice. As an important immunomodulatory drug, Intravenous immunoglobulin (IVIG) treatment significantly reduced the death rate of FM mice, inhibits the proliferation of virus and suppresses the hyperinflammatory state of inflamed heart. The expression of IFN-γ and Spi1 also decreased. These highlighted the therapeutic potential of IVIG and IFN-γ/Spi1 axis targeted therapy. The comprehensive spatiotemporal omics analysis, conducted pre- and post-FM treatment, has offered profound insights, significantly advancing our understanding and facilitating the strategic management of FM.

Contributor(s):Huihui Li, Xueting Chen.

Submitter:陈思琏(Silian Chen),technical support

Release date:2025-02-01

Updated:2025-02-01