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.

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.

Inferring cell communication using single-cell calcium spatiotemporal dynamics.

There are a limited number of experimental tools for non-destructively discovering cell communication events and . Here, using tissue-specific genetically encoded calcium indicator (GECI) mice, we describe a protocol for preprocessing GECI fluorescence time-series measured by live cell imaging or intravital microscopy, detecting peaks of single-cell calcium fluorescence transients, and inferring putative cell communication events from peak synchrony. For complete details on the use and execution of this protocol, please refer to Taghdiri et al.

Macrophage calcium reporter mice reveal immune cell communication and .

Cell communication underlies emergent functions in diverse cell types and tissues. Recent evidence suggests that macrophages are organized in communicating networks, but new tools are needed to quantitatively characterize the resulting cellular conversations. Here, we infer cell communication from spatiotemporal correlations of intracellular calcium dynamics that are non-destructively imaged across cell populations expressing genetically encoded calcium indicators.

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.

Hierarchically Patterned Polydopamine-Containing Membranes for Periodontal Tissue Engineering.

Periodontitis is a common chronic inflammatory disease that affects tooth-supporting tissues. We engineer a multifunctional periodontal membrane for the guided tissue regeneration of lost periodontal tissues. The major drawback of current periodontal membranes is the lack of tissue regeneration properties.