Project description:To investigate the microRNA regulated in the endocardial cells, we performed high-throughput profiling analysis using small RNA-Seq data obtained from Hdac3 CRISPR knockout mouse cardiac endothelail cells
Project description:To investigate the growth factors regulated in the endocardial cells, we performed gene expression profiling analysis using RNA-Seq data obtained from Hdac3 CRISPR knockout mouse cardiac endothelail cells
Project description:To investigate the signal communication from the endocardium to the trabecular myocardium, we performed single cell RNA sequencing (scRNA-seq) in E11.5 Hdac3 Tie2 knockout hearts and littermate control hearts
Project description:The ang1-Tie2 pathway is required for normal vascular development, but its molecular effectors are not well-defined during cardiac ontogeny. Here we show that endocardial specific attenuation of Tie2 results in mid-gestation lethality due to heart defects associated with a hyperplastic but simplified trabecular meshwork (fewer but thicker trabeculae). Reduced proliferation and production of endocardial cells (ECs) following endocardial loss of Tie2 results in decreased endocardial sprouting required for trabecular assembly and extension. The hyperplastic trabeculae result from enhanced proliferation of trabecular cardiomyocyte (CMs), which is associated with upregulation of Bmp10, increased retinoic acid (RA) signaling, and Erk1/2 hyperphosphorylation in the myocardium. Intriguingly, myocardial phenotypes in Tie2-cko hearts could be partially rescued by inhibiting in utero RA signaling with pan-retinoic acid receptor antagonist BMS493. These findings reveal two complimentary functions of endocardial Tie2 during ventricular chamber formation: ensuring normal trabeculation by supporting EC proliferation and sprouting, and preventing hypertrabeculation via suppression of RA signaling in trabecular CMs.
