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Quaking Is a Key Regulator of Endothelial Cell Differentiation,
Neovascularization, and Angiogenesis
#MMPMID28207177
Cochrane A
; Kelaini S
; Tsifaki M
; Bojdo J
; Vilŕ-González M
; Drehmer D
; Caines R
; Magee C
; Eleftheriadou M
; Hu Y
; Grieve D
; Stitt AW
; Zeng L
; Xu Q
; Margariti A
Stem Cells
2017[Apr]; 35
(4
): 952-966
PMID28207177
show ga
The capability to derive endothelial cell (ECs) from induced pluripotent stem
cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This
study elucidates the precise role of the RNA-binding protein Quaking isoform 5
(QKI-5) during EC differentiation from both mouse and human iPSCs (hiPSCs) and
dissects how RNA-binding proteins can improve differentiation efficiency toward
cell therapy for important vascular diseases. iPSCs represent an attractive
cellular approach for regenerative medicine today as they can be used to generate
patient-specific therapeutic cells toward autologous cell therapy. In this study,
using the model of iPSCs differentiation toward ECs, the QKI-5 was found to be an
important regulator of STAT3 stabilization and vascular endothelial growth factor
receptor 2 (VEGFR2) activation during the EC differentiation process. QKI-5 was
induced during EC differentiation, resulting in stabilization of STAT3 expression
and modulation of VEGFR2 transcriptional activation as well as VEGF secretion
through direct binding to the 3' UTR of STAT3. Importantly, mouse iPS-ECs
overexpressing QKI-5 significantly improved angiogenesis and neovascularization
and blood flow recovery in experimental hind limb ischemia. Notably, hiPSCs
overexpressing QKI-5, induced angiogenesis on Matrigel plug assays in vivo only 7
days after subcutaneous injection in SCID mice. These results highlight a clear
functional benefit of QKI-5 in neovascularization, blood flow recovery, and
angiogenesis. Thus, they provide support to the growing consensus that
elucidation of the molecular mechanisms underlying EC differentiation will
ultimately advance stem cell regenerative therapy and eventually make the
treatment of cardiovascular disease a reality. The RNA binding protein QKI-5 is
induced during EC differentiation from iPSCs. RNA binding protein QKI-5 was
induced during EC differentiation in parallel with the EC marker CD144.
Immunofluorescence staining showing that QKI-5 is localized in the nucleus and
stained in parallel with CD144 in differentiated ECs (scale bar?=?50 µm). Stem
Cells 2017 Stem Cells 2017;35:952-966.
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