PUBLICATION
Epigenetic landscape reveals MECOM as an endothelial lineage regulator
- Authors
- Lv, J., Meng, S., Gu, Q., Zheng, R., Gao, X., Kim, J.D., Chen, M., Xia, B., Zuo, Y., Zhu, S., Zhao, D., Li, Y., Wang, G., Wang, X., Meng, Q., Cao, Q., Cooke, J.P., Fang, L., Chen, K., Zhang, L.
- ID
- ZDB-PUB-230516-39
- Date
- 2023
- Source
- Nature communications 14: 23902390 (Journal)
- Registered Authors
- Fang, Longhou, Gu, Qilin, Kim, Jun-Dae
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Lineage/genetics
- Endothelial Cells*/metabolism
- Epigenesis, Genetic*
- Humans
- MDS1 and EVI1 Complex Locus Protein/genetics
- Regulatory Sequences, Nucleic Acid
- Transcription Factors/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 37185814 Full text @ Nat. Commun.
Citation
Lv, J., Meng, S., Gu, Q., Zheng, R., Gao, X., Kim, J.D., Chen, M., Xia, B., Zuo, Y., Zhu, S., Zhao, D., Li, Y., Wang, G., Wang, X., Meng, Q., Cao, Q., Cooke, J.P., Fang, L., Chen, K., Zhang, L. (2023) Epigenetic landscape reveals MECOM as an endothelial lineage regulator. Nature communications. 14:23902390.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping