Title: miRNA expression profiling in a human stem cell-based model as a tool for developmental neurotoxicity testing
Citation: CELL BIOLOGY AND TOXICOLOGY vol. 29 no. 4 p. 239-257
Publisher: SPRINGER
Publication Year: 2013
JRC N°: JRC81943
ISSN: 0742-2091
URI: http://link.springer.com/article/10.1007%2Fs10565-013-9250-5#
DOI: 10.1007/s10565-013-9250-5
Type: Articles in periodicals and books
Abstract: The main aim of this study was to evaluate whether microRNA (miRNA) profiling could be a useful tool for in vitro developmental neurotoxicity (DNT) testing. Therefore, to identify the possible DNT biomarkers among miRNAs, we have studied the changes in miRNA expressions in a mixed neuronal/glial culture derived from carcinoma pluripotent stem cells (NT2 cell line) after exposure to MetHgCl during the process of neuronal differentiation (2-36 DIV). The obtained results identified the presence of a miRNA signature which was specific for neural differentiation in the control culture and another for the response to MetHgCl-induced toxicity. In differentiated neuronal control cultures we observed the down-regulation of the stemness phenotype-linked miR-302 cluster and the over-expression of several miRNAs specific for neuronal differentiation (e.g. let-7, miR-125b and miR-132). In the cultures exposed to MetHgCl (400nM) we observed an over-expression of a signature composed of 5 miRNAs (miR-302b, miR-367, miR-372, miR-196b and miR-141) that are known to be involved in the regulation of developmental processes and cellular stress response mechanisms. Using gene ontology terms and pathway enrichment analysis of the validated targets of the miRNAs deregulated by the toxic treatment, the possible effect of MetHgCl exposure on signaling pathways involved in axon guidance and learning and memory processes was revealed. The obtained data suggest that miRNA profiling could provide simplified functional evaluation of the toxicity pathways involved in developmental neurotoxicity in comparison with the transcriptomics studies.
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