title: OCT4 Remodels the Phenotype and Promotes Angiogenesis of HUVECs by Changing the Gene Expression Profile.
abstract: It has been shown that forced expression of four mouse stem cell factors (OCT4, Sox2, Klf4, and c-Myc) changed the phenotype of rat endothelial cells to vascular progenitor cells. The present study aimed to explore whether the expression of OCT4 alone might change the phenotype of human umbilical vein endothelial cells (HUVECs) to endothelial progenitor cells and, if so, to examine the possible mechanism involved. A Matrigel-based in vitro angiogenesis assay was used to evaluate the angiogenesis of the cells; the gene expression profile was analyzed by an oligonucleotide probe-based gene array chip and validated by RT-QPCR. The cellular functions of the mRNAs altered by OCT4 were analyzed with Gene Ontology. We found that induced ectopic expression of mouse OCT4 in HUVECs significantly enhanced angiogenesis of the cells, broadly changed the gene expression profile and particularly increased the expression of CD133, CD34, and VEGFR2 (KDR) which are characteristic marker molecules for endothelial progenitor cells (EPCs). Furthermore by analyzing the cellular functions that were targeted by the mRNAs altered by OCT4 we found that stem cell maintenance and cell differentiation were among the top functional response targeted by up-regulated and down-regulated mRNAs upon forced expression of OCT4. These results support the argument that OCT4 remodels the phenotype of HUVECs from endothelial cells to EPCs by up-regulating the genes responsible for stem cell maintenance and down-regulating the genes for cell differentiation.
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.; 3. The Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mou
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yue
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
authors.affiliation: 2. Life Science Research Center, Beihua University, Jilin, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
mesh_terms: D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D004318:Doxycycline
keywords: Angiogenesis; Endothelial Progenitor Cells; Gene Expression; Human Umbilical Vein Endothelial Cells; Octamer-binding transcription factor 4.