PUBLICATION
Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis
- Authors
- Matrone, G., Xia, B., Chen, K., Denvir, M.A., Baker, A.H., Cooke, J.P.
- ID
- ZDB-PUB-210801-2
- Date
- 2021
- Source
- Proceedings of the National Academy of Sciences of the United States of America 118(31): (Journal)
- Registered Authors
- Keywords
- angiogenesis, differentiation, endothelial cells, epigenetic factors, zebrafish
- Datasets
- GEO:GSE149152
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Differentiation
- Embryo, Nonmammalian
- Endothelial Cells/physiology*
- Gene Expression Regulation, Developmental
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Humans
- Induced Pluripotent Stem Cells/physiology*
- Neovascularization, Physiologic/physiology*
- Platelet Endothelial Cell Adhesion Molecule-1/genetics
- Platelet Endothelial Cell Adhesion Molecule-1/metabolism
- Proto-Oncogene Protein c-fli-1/physiology*
- RNA-Seq
- Transcriptome
- Up-Regulation
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34330825 Full text @ Proc. Natl. Acad. Sci. USA
Citation
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):.
Abstract
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 RNA-sequencing 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- and low-fli1+ cells, high-fli1+ cells showed up-regulated expression of the zinc finger transcription factor PRDI-BF1 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping