title: Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.
abstract: Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans.
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahangno, Yuseong-gu, Daejeon 34141, Republic of Korea; Department of functional genomics, University of Science & Technology, 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Son
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.
authors.forename: Soojin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.
authors.forename: A-Young
authors.initials: AY
authors.lastname: Choi
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea.
authors.forename: Hyang-Ae
authors.initials: HA
authors.lastname: Lee
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea.
authors.forename: Ki-Suk
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahangno, Yuseong-gu, Daejeon 34141, Republic of Korea; Department of functional genomics, University of Science & Technology, 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Janghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: cwsong@kitox.re.kr.
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Song
authors.affiliation: Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: sjyoon@kitox.re.kr.
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies / Q000379:methods; D000066449:Human Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012834:Silver / Q000633:toxicity*
chemical_list: D035683:MicroRNAs; D012834:Silver
keywords: Developmental neurotoxicity; Gene expression profiling; Human embryonic stem cells derived neural cells; Nanotoxicity; Silver nanoparticles; miRNA profiling