Project description:Rapacz Familial Hypercholesterolemic (RFH) swine have been used extensively in the vascular biology field as a robust model of complex atherosclerotic lesions. However, the heart valves from RFH swine have not been evaluated and it is unknown whether these animals develop calcific aortic valve disease without dietary intervention. Histological assessment of heart valve leaflets isolated from juvenile and adult swine revealed RFH swine develop the early hallmarks of the disease at two years of age. The goal of this microarray study was to gain some insight into the cellular and molecular mechanisms that lead to the observed hallmarks and initiation of the disease. RNA samples from three juvenile wild type, and three juvenile and four adult RFH swine aortic valve leaflets were isolated, processed, and hybridized to Affymetrix GeneChip Porcine Genome microarrays according to the manufacturer's instructions. The mean expression values of each probeset in the adult RFH samples were compared to those in the juvenile RFH samples. Likewise, the mean expression values of each probeset in the juvenile RFH samples were compared to those in the juvenile wild type samples.
Project description:Rapacz Familial Hypercholesterolemic (RFH) swine have been used extensively in the vascular biology field as a robust model of complex atherosclerotic lesions. However, the heart valves from RFH swine have not been evaluated and it is unknown whether these animals develop calcific aortic valve disease without dietary intervention. Histological assessment of heart valve leaflets isolated from juvenile and adult swine revealed RFH swine develop the early hallmarks of the disease at two years of age. The goal of this microarray study was to gain some insight into the cellular and molecular mechanisms that lead to the observed hallmarks and initiation of the disease.
Project description:To systematically analyzed the genome-wide characterization of potential eccDNAs in mouse heart tissues, we peformed Circle-seq in embryonic, neonatal and adult mouse heart tissues.
Project description:Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies. Our findings unveil a Pitx2 postnatal arrhythmogenic function, novel Pitx2 target genes relevant to atrial fibrillation, and reveal that Pitx2 stabilizes the intercalated disc in postnatal atrium. Genomic occupancy profiling of transcriptional factor Pitx2 in postnatal heart.
Project description:The epicardium, a thin mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in species with elevated regenerative capacity like zebrafish. To dissect epicardial cell states and associated pro-regenerative functions, we performed single-cell RNA-sequencing and identified 7 epicardial cell clusters in adult zebrafish, with 3 of these clusters enhanced during regeneration. ECM components encoded by hapln1 paralogs label an enriched epicardial cell type that accumulates and encloses dedifferentiated and proliferating cardiomyocytes during regeneration. Genetic inactivation of hapln1b, or induced genetic depletion of hapln1a-expressing cells, disrupted cardiomyocyte proliferation and heart regeneration. hapln1a+ cells first emerge at the juvenile stage, when they associate with and are required for cardiogenic foci that direct growth of the juvenile heart. Our findings identify a subset of epicardial cells that emerges in post-embryonic animals and sponsors regions of active cardiomyogenesis during heart growth and regeneration