Integrative transcriptomic and epigenomic analysis identifies BCL6B as a novel regulator of human pluripotent stem cell to endothelial differentiation

Due to the inaccessibility of the early human embryo, little is known about the chromatin status during human endothelial development. In this study, we used the human pluripotent stem cell (hPSC) differentiation system to sketch the epigenomic roadmap of endothelial cell (EC) development. By profiling the open chromatin of stage-specific progenitor cells, we showed that the binding sites of developmentally important transcription factors open up in a highly coordinated manner along the endothelial differentiation continuum. Through the genome-wide association of key histone marks and accessible chromatin, we characterized broad H3K4me3 domains and three types of cis-regulatory elements (CREs) that correlated with the EC fate specification and differentiation stage. Finally, we identified BCL6B as a novel regulator of EC differentiation via integrative RNA-seq and epigenomic dataset analysis. Our findings provide a valuable resource to study the epigenetic regulation of EC development and dysfunction.