Epigenetic landscape reveals MECOM as an endothelial lineage regulator.
Jie LvShu MengQilin GuRongbin ZhengXinlei GaoJun-Dae KimMin ChenBo XiaYihan ZuoSen ZhuDongyu ZhaoYanqiang LiGuangyu WangXin WangQingshu MengQi CaoJohn P CookeLonghou FangKaifu ChenLili ZhangPublished in: Nature communications (2023)
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.
Keyphrases
- single cell
- endothelial cells
- rna seq
- high throughput
- high glucose
- vascular endothelial growth factor
- genome wide
- gene expression
- dna methylation
- signaling pathway
- transcription factor
- induced pluripotent stem cells
- induced apoptosis
- dna damage
- genome wide identification
- mesenchymal stem cells
- cell therapy
- oxidative stress