Epigenomic landscape of endothelial differentiation from human pluripotent stem cells

We performed transcriptome, open chromatin and genome binding of histone H3K4me3 H3K27ac, and H3K27me3 profiling of different endothelial populations during human pluripotent stem cell differentiation. Through integrative analysis, we identified transcription factor BCL6B as a novel regulator of arterial and venous endothelial cell fate. We also generated and characterized the transcriptome and chromatin state of BCL6B KO hECs to reveal the mechanism of its function. Methods: undifferentiated hESC (H1) cells, vascular mesoderm cells (VMCs), endothelial progenitor cells (EPCs), and endothelial cells (ECs) were sorted. Transcriptome profiling was done using the SMART-seq2 protocol; ATAC-seq and CUT&Tag methods were used to profile the chromatin accessibility and the genome-wide binding of histone H3K4me3, H3K27ac, H3K27me3 marks. BCL6B KO ECs were generated and the change in global gene expression was investigated by RNA-seq. ChIP-seq was performed to reveal the binding sequences of BCL6B. Results: By integrative analysis the transcriptome and epigenetic landscape of undifferentiated hESC (H1) cells, vascular mesoderm cells (VMCs), endothelial progenitor cells (EPCs), and endothelial cells (ECs). We depicted the epigenomic roadmap of human EC fate establishment, and identified BCL6B as a novel regulator of EC fate. We also characterized the differentially-expressed genes in wide-type and BCL6B knock-out ECs, inferred the potential target genes of BCL6B and the mechanism of BCL6B function. Conclusions: This study depicted the epigenomic lanscape of hPSC-EC differentiation, predicted transcription factors involved in EC fate specification and uncovered that BCL6B is a novel regulator of arterial and venous EC fate decision.