@article{319a3905fbe74669ace864467657b7a7,
title = "Endothelial angiogenesis is directed by RUNX1T1-regulated VEGFA, BMP4 and TGF-β2 expression",
abstract = "Tissue angiogenesis is intimately regulated during embryogenesis and postnatal development. Defected angiogenesis contributes to aberrant development and is the main complication associated with ischemia-related diseases. We previously identified the increased expression of RUNX1T1 in umbilical cord blood-derived endothelial colony-forming cells (ECFCs) by gene expression microarray. However, the biological relevance of RUNX1T1 in endothelial lineage is not defined clearly. Here, we demonstrate RUNX1T1 regulates the survival, motility and tube forming capability of ECFCs and EA.hy926 endothelial cells by loss-and gain-of function assays, respectively. Second, embryonic vasculatures and quantity of bone marrow-derived angiogenic progenitors are found to be reduced in the established Runx1t1 heterozygous knockout mice. Finally, a central RUNX1T1-regulated signature is uncovered and VEGFA, BMP4 as well as TGF-β2 are demonstrated to mediate RUNX1T1-orchested angiogenic activities. Taken together, our results reveal that RUNX1T1 serves as a common angiogenic driver for vaculogenesis and functionality of endothelial lineage cells. Therefore, the discovery and application of pharmaceutical activators for RUNX1T1 will improve therapeutic efficacy toward ischemia by promoting neovascularization.",
author = "Liao, {Ko Hsun} and Chang, {Shing Jyh} and Chang, {Hsin Chuan} and Chien, {Chen Li} and Huang, {Tse Shun} and Feng, {Te Chia} and Lin, {Wen Wei} and Shih, {Chuan Chi} and Yang, {Muh Hwa} and Yang, {Shung Haur} and Lin, {Chi Hung} and Hwang, {Wei Lun} and Lee, {Oscar K.}",
note = "Funding Information: The authors dedicate this work to the memory of Professor Hsei-Wei Wang (Apr. 1969-Sep. 2015). Dr. Hsei-Wei Wang focused on bioinformatics and molecular biology research; without his long-term devotion to EPC research this paper could not have been completed. The authors would like to thank Dr. Tzong-Shyuan Lee and Dr. Po-Hsun Huang for their advice and helpful comments. The authors also acknowledge the technical services provided by the Microarray & Gene Expression Analysis Core Facility and Instrument Resource Center of the National Yang-Ming University. The Runx1t1 knock-out mice were generated under the supervision of the Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, National Science Council (NSC) and the Gene Knockout Mouse Core Laboratory of National Taiwan University Center of Genomic Medicine. The authors also acknowledge the technical supports provided by Flow cytometry Core Facility of National Yang Ming University and Imaging Core Facility of Nanotechnology of the UST-YMU. This work is supported by Ministry of Science and Technology (MOST; 104-2321-B-101-027 to S.H.Y; 103-2314-B-010-053-MY3 to O.K.L; 104-0210-01-09-02, and 103-2633-H-010-001 to M.H.Y; and 105-2320-B-038-009-MY2 to W.L.H), Yuan{\textquoteright}s General Hospital (106YGH-TMU-02 to W.L.H), Hsinchu Mackay Memorial Hospital (MMH-HB-10614 to C.C.S) and Taipei Medical University (TMU104-AE1-B11 to W.L.H). Publisher Copyright: {\textcopyright} 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.",
year = "2017",
month = jun,
day = "1",
doi = "10.1371/journal.pone.0179758",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",
}