Epigenetic landscape reveals MECOM as an endothelial lineage regulator

Jie Lv; Shu Meng; Qilin Gu; Rongbin Zheng; Xinlei Gao; Jun dae Kim; Min Chen; Bo Xia; Yihan Zuo; Sen Zhu; Dongyu Zhao; Yanqiang Li; Guangyu Wang; Xin Wang; Qingshu Meng; Qi Cao; John P. Cooke; Longhou Fang; Kaifu Chen; Lili Zhang

doi:10.1038/s41467-023-38002-w

Epigenetic landscape reveals MECOM as an endothelial lineage regulator

Jie Lv, Shu Meng, Qilin Gu, Rongbin Zheng, Xinlei Gao, Jun dae Kim, Min Chen, Bo Xia, Yihan Zuo, Sen Zhu, Dongyu Zhao, Yanqiang Li, Guangyu Wang, Xin Wang, Qingshu Meng, Qi Cao, John P. Cooke, Longhou Fang, Kaifu Chen, Lili Zhang

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Article number	2390
Pages (from-to)	2390
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38002-w
State	Published - Apr 25 2023

Keywords

Animals
Humans
Cell Differentiation/genetics
Cell Lineage/genetics
Endothelial Cells/metabolism
Epigenesis, Genetic
MDS1 and EVI1 Complex Locus Protein/genetics
Regulatory Sequences, Nucleic Acid
Transcription Factors/metabolism
Zebrafish/genetics

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-023-38002-w

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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(1), 2390. Article 2390. https://doi.org/10.1038/s41467-023-38002-w

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title = "Epigenetic landscape reveals MECOM as an endothelial lineage regulator",

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.",

keywords = "Animals, Humans, Cell Differentiation/genetics, Cell Lineage/genetics, Endothelial Cells/metabolism, Epigenesis, Genetic, MDS1 and EVI1 Complex Locus Protein/genetics, Regulatory Sequences, Nucleic Acid, Transcription Factors/metabolism, Zebrafish/genetics",

author = "Jie Lv and Shu Meng and Qilin Gu and Rongbin Zheng and Xinlei Gao and Kim, {Jun dae} and Min Chen and Bo Xia and Yihan Zuo and Sen Zhu and Dongyu Zhao and Yanqiang Li and Guangyu Wang and Xin Wang and Qingshu Meng and Qi Cao and Cooke, {John P.} and Longhou Fang and Kaifu Chen and Lili Zhang",

note = "Funding Information: This work is supported by grants from NIH/NIGMS (R01GM125632 and R01GM138407 to K.C.) and NIH/NHLBI (R01HL133254 to J.C. and K.C.; R01HL148338 to J.C. and K.C.; 1R01HL132155 to L.F.; and R01HL155632 to L.Z.), and Additional Ventures (Single Ventricle Research Foundation to L.Z.), George and Angelina foundation to L.F., and Cancer Prevention Research Institute of Texas (CPRIT) grants RP150611 and RP170002. Q.C. is supported by U.S. Department of Defense (W81XWH-15-1-0639 and W81XWH-17-1-0357), American Cancer Society (TBE-128382) and NIH/NCI (R01CA208257). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = apr,

day = "25",

doi = "10.1038/s41467-023-38002-w",

language = "English (US)",

volume = "14",

pages = "2390",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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TY - JOUR

T1 - Epigenetic landscape reveals MECOM as an endothelial lineage regulator

AU - Lv, Jie

AU - Meng, Shu

AU - Gu, Qilin

AU - Zheng, Rongbin

AU - Gao, Xinlei

AU - Kim, Jun dae

AU - Chen, Min

AU - Xia, Bo

AU - Zuo, Yihan

AU - Zhu, Sen

AU - Zhao, Dongyu

AU - Li, Yanqiang

AU - Wang, Guangyu

AU - Wang, Xin

AU - Meng, Qingshu

AU - Cao, Qi

AU - Cooke, John P.

AU - Fang, Longhou

AU - Chen, Kaifu

AU - Zhang, Lili

N1 - Funding Information: This work is supported by grants from NIH/NIGMS (R01GM125632 and R01GM138407 to K.C.) and NIH/NHLBI (R01HL133254 to J.C. and K.C.; R01HL148338 to J.C. and K.C.; 1R01HL132155 to L.F.; and R01HL155632 to L.Z.), and Additional Ventures (Single Ventricle Research Foundation to L.Z.), George and Angelina foundation to L.F., and Cancer Prevention Research Institute of Texas (CPRIT) grants RP150611 and RP170002. Q.C. is supported by U.S. Department of Defense (W81XWH-15-1-0639 and W81XWH-17-1-0357), American Cancer Society (TBE-128382) and NIH/NCI (R01CA208257). Publisher Copyright: © 2023, The Author(s).

PY - 2023/4/25

Y1 - 2023/4/25

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Cell Differentiation/genetics

KW - Cell Lineage/genetics

KW - Endothelial Cells/metabolism

KW - Epigenesis, Genetic

KW - MDS1 and EVI1 Complex Locus Protein/genetics

KW - Regulatory Sequences, Nucleic Acid

KW - Transcription Factors/metabolism

KW - Zebrafish/genetics

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U2 - 10.1038/s41467-023-38002-w

DO - 10.1038/s41467-023-38002-w

M3 - Article

C2 - 37185814

AN - SCOPUS:85154594187

SN - 2041-1723

VL - 14

SP - 2390

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2390

ER -

Epigenetic landscape reveals MECOM as an endothelial lineage regulator

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Keywords

ASJC Scopus subject areas

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