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2015 ; 112
(1
): 160-5
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ETS transcription factor ETV2 directly converts human fibroblasts into functional
endothelial cells
#MMPMID25540418
Morita R
; Suzuki M
; Kasahara H
; Shimizu N
; Shichita T
; Sekiya T
; Kimura A
; Sasaki K
; Yasukawa H
; Yoshimura A
Proc Natl Acad Sci U S A
2015[Jan]; 112
(1
): 160-5
PMID25540418
show ga
Transplantation of endothelial cells (ECs) is a promising therapeutic approach
for ischemic disorders. In addition, the generation of ECs has become
increasingly important for providing vascular plexus to regenerated organs, such
as the liver. Although many attempts have been made to generate ECs from
pluripotent stem cells and nonvascular cells, the minimum number of transcription
factors that specialize in directly inducing vascular ECs remains undefined.
Here, by screening 18 transcription factors that are important for both
endothelial and hematopoietic development, we demonstrate that ets variant 2
(ETV2) alone directly converts primary human adult skin fibroblasts into
functional vascular endothelial cells (ETVECs). In coordination with endogenous
FOXC2 in fibroblasts, transduced ETV2 elicits expression of multiple key
endothelial development factors, including FLI1, ERG, and TAL1, and induces
expression of endothelial functional molecules, including EGFL7 and von
Willebrand factor. Consequently, ETVECs exhibits EC characteristics in vitro and
forms mature functional vasculature in Matrigel plugs transplanted in NOD SCID
mice. Furthermore, ETVECs significantly improve blood flow recovery in a hind
limb ischemic model using BALB/c-nu mice. Our study indicates that the creation
of ETVECs provides further understanding of human EC development induced by ETV2.