Gene-environment interaction between Notch1 and oxidative stress disrupts cardiac developmental pathways

The majority of congenital heart disease cases lack a definitive cause, suggesting the role of gene-environment interactions (GxE) in disease pathogenesis. Maternal diabetes mellitus (matDM) is among the most prevalent environmental risk factors for CHD and matDM associated oxidative stress is known to disrupt cardiac development. Here, we demonstrate that NOTCH1 haploinsufficient endothelial cells have an altered transcriptomic response to oxidative stress compared to control endothelial cells, with an exacerbated effect on gene regulatory networks crucial for endocardial cushion morphogenesis. Overall design: Comparative gene expression profiling analysis of RNA-seq data for NOTCH1WT and NOTCH1+/- iPSC derived endothelial cells in normal culture conditions and with exposure to 50 micromolar hydrogen peroxide for 4 days.