IFN-? activates an immune-like regulatory network in the cardiac vascular endothelium

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-?) during myocarditis. We generate RNA-seq and ATAC-seq for four CVPCs that were treated with IFN-? and compare them with paired untreated controls. Transcriptional differences after treatment show that IFN-? initiates an innate immune cell-like response in the vascular cardiac endothelium. IFN-? 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-? 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. Overall design: RNA-seq and ATAC-seq was generated for four iPSC-derived cardiovascular progenitor cells (CVPCs) stimulated with 100nM IFNg. Both stimulated and paired control CVPCs have molecular data resulting in 16 FASTQ files.