Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

Introduction: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy.

Materials And Methods: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site.

Single-cell and spatial transcriptomics of the infarcted heart define the dynamic onset of the border zone in response to mechanical destabilization.

The border zone (BZ) of the infarcted heart is a geographically complex and biologically enigmatic interface separating poorly perfused infarct zones (IZs) from remote zones (RZs). The cellular and molecular mechanisms of myocardial BZs are not well understood because microdissection inevitably combines them with uncontrolled amounts of RZs and IZs. Here, we use single-cell/nucleus RNA sequencing, spatial transcriptomics and multiplexed RNA fluorescence in situ hybridization to redefine the BZ based on cardiomyocyte transcriptomes.

NOD-like receptor protein 3 activation causes spontaneous inflammation and fibrosis that mimics human NASH.

Background And Aims: The NOD-like receptor protein 3 (NLRP3) inflammasome is a central contributor to human acute and chronic liver disease, yet the molecular and cellular mechanisms by which its activation precipitates injury remain incompletely understood. Here, we present single cell transcriptomic profiling of livers from a global transgenic tamoxifen-inducible constitutively activated Nlrp3 mutant mouse, and we investigate the changes in parenchymal and nonparenchymal liver cell gene expression that accompany inflammation and fibrosis.

Approach And Results: Our results demonstrate that NLRP3 activation causes chronic extramedullary myelopoiesis marked by myeloid progenitors that differentiate into proinflammatory neutrophils, monocytes, and monocyte-derived macrophages.