Transcriptomic and methylomic analysis reveal the toxicological effect of 2,3,7,8-Tetrachlorodibenzodioxin on human embryonic stem cell.

Autor: Lai KP; Department of Chemistry, City University of Hong Kong, China., Li JW; Department of Chemistry, City University of Hong Kong, China; Partner State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, China., Chan TF; Partner State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, China., Chen A; Department of Obstetrics and Gynaecology, The University of Hong Kong, China., Lee CYL; Department of Obstetrics and Gynaecology, The University of Hong Kong, China., Yeung WSB; Department of Obstetrics and Gynaecology, The University of Hong Kong, China., Wong CKC; Partner State Key Laboratory of Environmental and Biological Analysis, Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, China. Electronic address: ckcwong@hkbu.edu.hk.
Jazyk: angličtina
Zdroj: Chemosphere [Chemosphere] 2018 Sep; Vol. 206, pp. 663-673. Date of Electronic Publication: 2018 May 10.
DOI: 10.1016/j.chemosphere.2018.05.058
Abstrakt: Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function. But the effect of dioxin exposure in early stage of fetal development is still largely unknown. In this report, we used the human embryonic stem cell (hESC) line, VAL-3, as a model, together with Methyl-CpG Binding Domain (MBD) protein-enriched genome sequencing and transcriptome sequencing (RNA-seq), in order to determine the dynamic changes of the epigenetic landscape and transcriptional dysregulation in hESC upon dioxin exposure. The bioinformatics analyses including the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis and Ingenuity Pathway Analysis (IPA) highlighted the predisposed neural, hepatic, cardiac and metabolic toxicological effects of dioxin during the fetal development.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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