The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Spatiotemporal transcriptomics elucidates the pathogenesis of fulminant viral myocarditis
Open accessAbstract
Fulminant myocarditis (FM) is a severe inflammatory condition of the myocardium that often results in sudden death, particularly in young individuals. In this study, we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3 (CVB3)-induced FM in A/J mice, spanning seven distinct time points pre- and post-treatment. Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection. This triggers the activation of macrophages, initiating a cascade of inflammation. Subsequently, pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium, driving tissue damage. We also identified Cd8 + effector T cells as key mediators of cardiomyocyte injury. These cells release cytotoxic molecules, particularly IFN-γ, which modulates the expression of Spi1 , a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression. Therapeutic interventions targeting the IFN-γ/ Spi1 axis demonstrated significant efficacy in FM models. Notably, intravenous immunoglobulin (IVIG) treatment reduced mortality, suppressed viral proliferation, and mitigated the hyperinflammatory state of FM. IVIG therapy also downregulated IFN-γ and Spi1 expression, underscoring its immunomodulatory and therapeutic potential. This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets, paving the way for more effective management strategies for this life-threatening condition.
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“However, both models demonstrate pivotal roles for myeloid–fibroblast communication and patchy spatial patterns of injury, underscoring shared pathways in tissue remodelling.”
From Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics. (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Both viral models, analyzed with spatial and single-cell transcriptomics, reveal pronounced spatial heterogeneity of myocardial injury, dense infiltration by immune cells (notably T cells and macrophages), and strong upregulation of interferon-related antiviral pathways.”
From Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics. (2025) · cites this paper as [13]
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“In contrast, our autoimmune (EAM) model recapitulates immune-driven tissue damage and fibroblast activation, but lacks the direct cytopathic effects and robust early interferon signatures seen in viral myocarditis.”
From Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics. (2025) · cites this paper as [13]
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“Importantly, recent results from Li et al. highlight the IFN-γ/Spi1 axis and mesothelial infection as unique drivers in fulminant viral myocarditis, with translational implications for immunomodulatory therapies [13].”
From Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics. (2025) · cites this paper as [13]
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Research works printed but not linked: 1
- Li, M. et al. StereoCell enables highly accurate single-cell segmentation for spatial transcriptomics. bioRxiv, 2023.2002.2028.530414 (2023).
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Xu, J., Chen, X., Guan, X., Zhang, H., Liu, Y., & Zhang, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1643502 · Cited by 12
Self-citationWu, X., Xu, W., Lin, D., Sun, L., Loo, L., Dai, J., & Cao, G. (2025) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2025.09.003 · Cited by 11
Zhuang, Y., Yan, Y., Zheng, W., Rao, X., Jiang, J., Li, H., & Wang, D. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103970 · Cited by 7
Self-citationCardiac Macrophages across Space and Time: Roles in Homeostasis, Disease, and Remodeling
Shrestha, S., & Dick, S. A. (2026) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2026.02.025 · Cited by 7
Charting the cardiac landscape: Advances in spatial transcriptomics for heart biology
Farah, E. N., Diaz, J. T., Bloomekatz, J. E., & Chi, N. C. (2025) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2025.103648 · Cited by 9
Metadata
- Authors
- Li, H., Chen, X., Wang, J. J., Shen, J., Abuduwufuer, K., Zhang, Z., Dong, Z., Wen, Z., He, J., Chen, S., Li, W., Chen, C., Li, F., Fang, X., & Wang, D. W.
- Affiliations
- Tongji Hospital (CN)
- Chinese Academy of Sciences (CN)
- BGI Research (CN)
- MGI (CN)
- Guangzhou University of Chinese Medicine (CN)
- Corresponding author
- Fang, Xiaodong
- Wang, Dao Wen
- ORCID
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2025-02-10
- Volume
- 10
- Issue
- 1
- Pages
- 59-59
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC11808084
- OpenAlex
- W4407284214
- Cited by
- 40
- References
- 65
- Citations by year
- 2026: 24 · 2025: 16
- FWCI
- 27.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (82330010, 82241034)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Takotsubo Cardiomyopathy and Associated Phenomena
- Keywords
- fulminant myocarditis, coxsackievirus B3, mesothelial cells, macrophage activation, T cell infiltration, CD8+ effector T cells, cardiomyocyte injury, interferon-gamma, PU.1, intravenous immunoglobulin, hyperinflammation, A/J mice, sudden cardiac death
- MeSH terms
- Animals, Coxsackievirus Infections, Disease Models, Animal, Humans, Interferon-gamma, Macrophages, Male, Myocarditis, Proto-Oncogene Proteins, Trans-Activators, Immunoglobulins, Intravenous, CD8-Positive T-Lymphocytes, Enterovirus B, Human, Myocytes, Cardiac, Mice, Transcriptome
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