title: Reactive oxygen species regulate the quiescence of CD34-positive cells derived from human embryonic stem cells.
abstract: OBJECTIVE
  Reactive oxygen species (ROS) are involved in a wide range of cellular processes. However, few studies have examined the generation and function of ROS in human embryonic vascular development. In this study, the sources of ROS and their roles in the vascular differentiation of human embryonic stem cells (hESCs) were investigated.
  
  
  RESULTS
  During vascular differentiation of hESCs, CD34(+) cells had quiescence-related gene expression profiles and a large fraction of these cells were in G0 phase. In addition, levels of ROS, which were primarily generated through NOX4, were substantially higher in hESC-derived CD34(+) cells than in hESC-derived CD34(-) cells. To determine whether excess levels of ROS induce quiescence of hESC-derived CD34(+) cells, ROS levels were moderately reduced using selenium to enhance antioxidant activities of thioredoxin reductase and glutathione peroxidase. In comparison to untreated CD34(+) cells, selenium-treated CD34(+) cells exhibited changes in gene expression that favoured cell cycle progression, and had a greater proliferation and a smaller fraction of cells in G0 phase. Thus, selenium treatment increased the number of hESC-derived CD34(+) cells, thereby enhancing the efficiency with which hESCs differentiated into vascular endothelial and smooth muscle cells.
  
  
  CONCLUSIONS
  This study reveals that NOX4 produces ROS in CD34(+) cells during vascular differentiation of hESCs, and shows that modulation of ROS levels using antioxidants such as selenium may be a novel approach to increase the vascular differentiation efficiency of hESCs.
authors.affiliation: College of Pharmacy, Ajou University, San 5, Woncheon-Dong, Yeongtong-Gu, Suwon, Gyeonggi-do 443-749, Korea.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Song
authors.affiliation: College of Pharmacy, Ajou University, San 5, Woncheon-Dong, Yeongtong-Gu, Suwon, Gyeonggi-do 443-749, Korea.
authors.forename: Kyungjong
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Ajou University, San 5, Woncheon-Dong, Yeongtong-Gu, Suwon, Gyeonggi-do 443-749, Korea.
authors.forename: Jeong Joo
authors.initials: JJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.affiliation: College of Pharmacy, Ajou University, San 5, Woncheon-Dong, Yeongtong-Gu, Suwon, Gyeonggi-do 443-749, Korea wonhee.suh@gmail.com.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D012643:Selenium / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium
keywords: CD34; Human embryonic stem cells; Reactive oxygen species; Selenium; Vascular differentiation