IFN-γ activates an immune-like regulatory network in the cardiac vascular endothelium
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ABSTRACT: The regulatory mechanisms underlying the response to pro-inflammatory cytokines during myocarditis are poorly understood. Here, we use iPSC-derived cardiovascular progenitor cells (CVPCs) to model the response to interferon gamma (IFN-γ) during myocarditis. We generate RNA-seq and ATAC-seq for four CVPCs that were treated with IFN-γ and compare them with paired untreated controls. Transcriptional differences after treatment show that IFN-γ initiates an innate immune cell-like response in the vascular cardiac endothelium. IFN-γ treatment also shifts the CVPC transcriptome towards the adult coronary artery and aorta-like profile and expands the relative endothelial cell population in all four CVPC lines. Analysis of the accessible chromatin shows that IFN-γ is a potent chromatin remodeler and establishes an IRF-STAT immune-cell like regulatory network. Our findings reveal insights into the endothelial-specific protective mechanisms during myocarditis.
ORGANISM(S): Homo sapiens
PROVIDER: GSE263611 | GEO | 2024/07/12
REPOSITORIES: GEO
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