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DOI	10.1073/pnas.2008559118
	Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis
	Matrone G.; Xia B.; Chen K.; Denvir M.A.; Baker A.H.; Cooke J.P.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	A network of molecular factors drives the development, differentiation, and maintenance of endothelial cells. Friend leukemia integration 1 transcription factor (FLI1) is a bona fide marker of endothelial cells during early development. In zebrafish Tg(fli1:EGFP)y1,we identified two endothelial cell populations, high-fli1+ and low-fli1+, by the intensity of green fluorescent protein signal. By comparing RNAsequencing analysis of non-fli1 expressing cells (fli1-) with these two (fli1+) cell populations,we identified several up-regulated genes, not previously recognized as important, during endothelial development. Compared with fli1- A nd low-fli1+ cells, high-fli1+ cells showed up-regulated expression of the zinc finger transcription factor PRDIBF1 and RIZ homology domain containing 16 (prdm16). Prdm16 knockdown (KD) by morpholino in the zebrafish larva was associated with impaired angiogenesis and increased number of low-fli1+ cells at the expense of high-fli1+ cells. In addition, PRDM16 KD in endothelial cells derived from human-induced pluripotent stem cells impaired their differentiation and migration in vitro. Moreover, zebrafish mutants (mut) with loss of function for the oncogene LIM domain only 2 (lmo2) also showed reduced prdm16 gene expression combined with impaired angiogenesis. Prdm16 expression was reduced further in endothelial (CD31+) cells compared with CD31-cells isolated from lmo2-mutants (lmo2-mut) embryos. Chromatin immunoprecipitation-PCR demonstrated that Lmo2 binds to the promoter and directly regulates the transcription of prdm16. This work unveils a mechanism by which prdm16 expression is activated in endothelial cells by Lmo2 and highlights a possible therapeutic pathway by which to modulate endothelial cell growth and repair. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Angiogenesis; Differentiation; Endothelial cells; Epigenetic factors; Zebrafish
语种	英语
scopus关键词	messenger RNA; PRDIBF1 and RIZ homology domain containing 16; protein Lmo2; transcription factor Fli 1; unclassified drug; zinc finger protein; green fluorescent protein; platelet endothelial cell adhesion molecule 1; transcription factor Fli 1; transcriptome; zebrafish protein; angiogenesis; animal cell; Article; cell differentiation; cell isolation; cell migration; cell proliferation; chromatin immunoprecipitation; controlled study; CRISPR-CAS9 system; down regulation; embryo; endothelium cell; flow cytometry; fluorescence imaging; gene; genetic transcription; immunocytochemistry; immunohistochemistry; in vitro study; induced pluripotent stem cell; larva; lmo2 gene; mutant; nonhuman; phenotype; prdm16 gene; promoter region; protein binding; protein expression; real time polymerase chain reaction; RNA extraction; RNA sequencing; upregulation; Western blotting; zebra fish; angiogenesis; animal; gene expression regulation; genetics; human; metabolism; nonmammalian embryo; physiology; transgenic animal; Animals; Animals, Genetically Modified; Cell Differentiation; Embryo, Nonmammalian; Endothelial Cells; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Humans; Induced Pluripotent Stem Cells; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Protein c-fli-1; RNA-Seq; Transcriptome; Up-Regulation; Zebrafish; Zebrafish Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251084
作者单位	Houston Methodist Research Institute, Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston, TX 77030, United States; British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom; Houston Methodist Research Institute, Department of Cardiovascular Sciences, Center for Bioinformatics and Computational Biology, Houston, TX 77030, United States
推荐引用方式 GB/T 7714	Matrone G.,Xia B.,Chen K.,et al. Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis[J],2021,118(31).
APA	Matrone G.,Xia B.,Chen K.,Denvir M.A.,Baker A.H.,&Cooke J.P..(2021).Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Matrone G.,et al."Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).