Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP265 |
In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children | |
Wagner, Peter J.1,2; Park, Hae-Ryung1,2; Wang, Zhaoxi1; Kirchner, Rory3; Wei, Yongyue1; Su, Li1; Stanfield, Kirstie4; Guilarte, TomasR.4; Wright, Robert O.5; Christiani, David C.2; Lu, Quan1,2,6 | |
2017-04-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:4 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | BACKGROUND: Lead (Pb) adversely affects neurodevelopment in children. Neural stem cells (NSCs) play an essential role in shaping the developing brain, yet little is known about how Pb perturbs NSC functions and whether such perturbation contributes to impaired neurodevelopment. OBJECTIVES: We aimed to identify Pb-induced transcriptomic changes in NSCs and to link these changes to neurodevelopmental outcomes in children who were exposed to Pb. METHODS: We performed RNA-seq-based transcriptomic profiling in human NSCs treated with 1 mu M Pb. We used qRT-PCR, Western blotting, ELISA, and ChIP (chromatin immuno-precipitation) to characterize Pb-induced gene up-regulation. Through interrogation of a genomewide association study, we examined the association of gene variants with neurodevelopment outcomes in the ELEMENT birth cohort. RESULTS: We identified 19 genes with significantly altered expression, including many known targets of NRF2-the master transcriptional factor for the oxidative stress response. Pb induced the expression of SPP1 (secreted phosphoprotein 1), which has known neuroprotective effects. We demonstrated that SPP1 is a novel direct NRF2 target gene. Single nucleotide polymorphisms (SNPs) (rs12641001) in the regulatory region of SPP1 exhibited a statistically significant association (p=0.005) with the Cognitive Development Index (CDI). CONCLUSION: Our findings revealed that Pb induces an NRF2-dependent transcriptional response in neural stem cells and identified SPP1 up-regulation as a potential novel mechanism linking Pb exposure with neural stem cell function and neurodevelopment in children. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000397904400036 |
WOS关键词 | DELTA-AMINOLEVULINIC-ACID ; B-DEPENDENT PATHWAY ; MATERNAL BONE-LEAD ; BLOOD LEAD ; OSTEOPONTIN INCREASES ; BRAIN-INJURY ; CONFERRING PROTECTION ; MICROARRAY ANALYSIS ; OXIDATIVE STRESS ; PROGENITOR CELLS |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/23936 |
专题 | 资源环境科学 |
作者单位 | 1.Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA; 2.Harvard TH Chan Sch Publ Hlth, Program Mol & Integrat Physiol Sci, Boston, MA USA; 3.Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA; 4.Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA; 5.Mt Sinai Sch Med, Dept Preventat Med, New York, NY USA; 6.Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA |
推荐引用方式 GB/T 7714 | Wagner, Peter J.,Park, Hae-Ryung,Wang, Zhaoxi,et al. In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(4). |
APA | Wagner, Peter J..,Park, Hae-Ryung.,Wang, Zhaoxi.,Kirchner, Rory.,Wei, Yongyue.,...&Lu, Quan.(2017).In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children.ENVIRONMENTAL HEALTH PERSPECTIVES,125(4). |
MLA | Wagner, Peter J.,et al."In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children".ENVIRONMENTAL HEALTH PERSPECTIVES 125.4(2017). |
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