Genome-wide identification of endothelial cell-enriched genes in the mouse embryo

Haruka Takase; Ken Matsumoto; Rie Yamadera; Yoshiaki Kubota; Ayaka Otsu; Rumiko Suzuki; Hiroyuki Ishitobi; Hiromi Mochizuki; Takahiro Kojima; Shingo Takano; Kazuhiko Uchida; Satoru Takahashi; Masatsugu Ema

doi:10.1182/blood-2011-12-398156

Genome-wide identification of endothelial cell-enriched genes in the mouse embryo

Blood. 2012 Jul 26;120(4):914-23. doi: 10.1182/blood-2011-12-398156. Epub 2012 Apr 25.

Authors

Haruka Takase¹, Ken Matsumoto, Rie Yamadera, Yoshiaki Kubota, Ayaka Otsu, Rumiko Suzuki, Hiroyuki Ishitobi, Hiromi Mochizuki, Takahiro Kojima, Shingo Takano, Kazuhiko Uchida, Satoru Takahashi, Masatsugu Ema

Affiliation

¹ Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan.

PMID: 22535667
DOI: 10.1182/blood-2011-12-398156

Abstract

The early blood vessels of the embryo and yolk sac in mammals develop by aggregation of de novo-forming angioblasts into a primitive vascular plexus, which then undergoes a complex remodeling process. Angiogenesis is also important for disease progression in the adult. However, the precise molecular mechanism of vascular development remains unclear. It is therefore of great interest to determine which genes are specifically expressed in developing endothelial cells (ECs). Here, we used Flk1-deficient mouse embryos, which lack ECs, to perform a genome-wide survey for genes related to vascular development. We identified 184 genes that are highly enriched in developing ECs. The human orthologs of most of these genes were also expressed in HUVECs, and small interfering RNA knockdown experiments on 22 human orthologs showed that 6 of these genes play a role in tube formation by HUVECs. In addition, we created Arhgef15 knockout and RhoJ knockout mice by a gene-targeting method and found that Arhgef15 and RhoJ were important for neonatal retinal vascularization. Thus, the genes identified in our survey show high expression in ECs; further analysis of these genes should facilitate our understanding of the molecular mechanisms of vascular development in the mouse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism*
Carcinoma, Lewis Lung / blood supply
Carcinoma, Lewis Lung / metabolism
Carcinoma, Lewis Lung / pathology
Cells, Cultured
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism*
Endothelium, Vascular / cytology
Endothelium, Vascular / metabolism*
Female
GTP Phosphohydrolases / antagonists & inhibitors
GTP Phosphohydrolases / physiology
Gene Expression Profiling*
Genome*
Guanine Nucleotide Exchange Factors / antagonists & inhibitors
Guanine Nucleotide Exchange Factors / physiology
Human Umbilical Vein Endothelial Cells / cytology
Human Umbilical Vein Endothelial Cells / metabolism
Immunoenzyme Techniques
In Situ Hybridization
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Neovascularization, Physiologic*
Oligonucleotide Array Sequence Analysis
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Retina / cytology
Retina / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor Receptor-2 / physiology*
rho GTP-Binding Proteins

Substances

Biomarkers
Guanine Nucleotide Exchange Factors
RNA, Messenger
RNA, Small Interfering
Rhoj protein, mouse
Vascular Endothelial Growth Factor Receptor-2
GTP Phosphohydrolases
rho GTP-Binding Proteins