Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/25312
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dc.contributor.authorKrug, AK-
dc.contributor.authorKolde, R-
dc.contributor.authorGaspar, JA-
dc.contributor.authorRempel, E-
dc.contributor.authorBalmer, NV-
dc.contributor.authorMeganathan, K-
dc.contributor.authorVojnits, K-
dc.contributor.authorBaquié, M-
dc.contributor.authorWaldmann, T-
dc.contributor.authorEnsenat-Waser, R-
dc.contributor.authorJagtap, S-
dc.contributor.authorEvans, RM-
dc.contributor.authorJulien, S-
dc.contributor.authorPeterson, H-
dc.contributor.authorZagoura, D-
dc.contributor.authorKadereit, S-
dc.contributor.authorGerhard, D-
dc.contributor.authorSotiriadou, I-
dc.contributor.authorHeke, M-
dc.contributor.authorNatarajan, K-
dc.contributor.authorHenry, M-
dc.contributor.authorWinkler, J-
dc.contributor.authorMarchan, R-
dc.contributor.authorStoppini, L-
dc.contributor.authorBosgra, S-
dc.contributor.authorWesterhout, J-
dc.contributor.authorVerwei, M-
dc.contributor.authorVilo, J-
dc.contributor.authorKortenkamp, A-
dc.contributor.authorHescheler, J-
dc.contributor.authorHothorn, L-
dc.contributor.authorBremer, S-
dc.contributor.authorVan Thriel, C-
dc.contributor.authorKrause, KH-
dc.contributor.authorHengstler, JG-
dc.contributor.authorRahnenführer, J-
dc.contributor.authorLeist, M-
dc.contributor.authorSachinidis, A-
dc.date.accessioned2022-10-13T12:19:01Z-
dc.date.available2013-01-01-
dc.date.available2022-10-13T12:19:01Z-
dc.date.issued2013-01-01-
dc.identifier.citationKrug, A.K., Kolde, R., Gaspar, J.A. et al. (2013) Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol., Vol. 87 (1), pp. 123 - 143. https://doi.org/10.1007/s00204-012-0967-3en_US
dc.identifier.issn0340-5761-
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/25312-
dc.description.abstractDevelopmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication. The fields of DNT/RT would greatly benefit from in vitro tests that allow the identification of toxicant-induced changes of the cellular proteostasis, or of its underlying transcriptome network. Therefore, the 'human embryonic stem cell (hESC)- derived novel alternative test systems (ESNATS)' European commission research project established RT tests based on defined differentiation protocols of hESC and their progeny. Valproic acid (VPA) and methylmercury (MeHg) were used as positive control compounds to address the following fundamental questions: (1) Does transcriptome analysis allow discrimination of the two compounds? (2) How does analysis of enriched transcription factor binding sites (TFBS) and of individual probe sets (PS) distinguish between test systems? (3) Can batch effects be controlled? (4) How many DNA microarrays are needed? (5) Is the highest non-cytotoxic concentration optimal and relevant for the study of transcriptome changes? VPA triggered vast transcriptional changes, whereas MeHg altered fewer transcripts. To attenuate batch effects, analysis has been focused on the 500 PS with highest variability. The test systems differed significantly in their responses (\20 % overlap). Moreover, within one test system, little overlap between the PS changed by the two compounds has been observed. However, using TFBS enrichment, a relatively large 'common response' to VPA and MeHg could be distinguished from 'compound-specific' responses. In conclusion, the ESNATS assay battery allows classification of human DNT/RT toxicants on the basis of their transcriptome profiles.en_US
dc.description.sponsorshipFP7 project ESNATS, the DFG and the Doerenkamp-Zbinden Foundation.en_US
dc.format.extent123 - 143-
dc.publisherSpringeren_US
dc.rightsOpen Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.-
dc.rights.urihttps://creativecommons.org/licenses/by/2.0-
dc.subjectMethylmercuryen_US
dc.subjectValproic aciden_US
dc.subjectTranscription factoren_US
dc.subjectReproductive toxicityen_US
dc.subjectAlternative testing strategiesen_US
dc.titleHuman embryonic stem cell-derived test systems for developmental neurotoxicity: A transcriptomics approachen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1007/s00204-012-0967-3-
dc.relation.isPartOfArchives of Toxicology-
pubs.issue1-
pubs.publication-statusPublished-
pubs.volume87-
dc.identifier.eissn1432-0738-
Appears in Collections:Dept of Life Sciences Research Papers

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