Epigenetic landscape reveals MECOM as an endothelial lineage regulator

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator. Errors in vascular development are associated with several congenital defects. Here they systematically investigated the epigenetic landscape of the endothelial lineage and found that MECOM depletion impairs endothelial cell differentiation and angiogenesis.

Automated summary

A comprehensive understanding of the lineage specification of endothelial cells is crucial for cardiovascular regenerative medicine. Recent studies have revealed the preferential regulation of cell identity genes by unique epigenetic signatures. In this study, we investigated the epigenetic landscape of endothelial cell lineage and identified MECOM as a key regulator.