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Human embryonic stem cell-derived test systems for developmental neurotoxicity : a transcriptomics approach

Human embryonic stem cell-derived test systems for developmental neurotoxicity : a transcriptomics approach

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Prüfsumme: MD5:c610c299b710e7e12e02ffb823fabdbe

KRUG, Anne-Kathrin, Raivo KOLDE, John A. GASPAR, Eugen REMPEL, Nina V. BALMER, Tanja WALDMANN, Suzanne KADEREIT, Jan G. HENGSTLER, Jörg RAHNENFÜHRER, Marcel LEIST, Agapios SACHINIDIS, 2013. Human embryonic stem cell-derived test systems for developmental neurotoxicity : a transcriptomics approach. In: Archives of Toxicology. 87(1), pp. 123-143. ISSN 0340-5761. eISSN 1432-0738

@article{Krug2013-01Human-24385, title={Human embryonic stem cell-derived test systems for developmental neurotoxicity : a transcriptomics approach}, year={2013}, doi={10.1007/s00204-012-0967-3}, number={1}, volume={87}, issn={0340-5761}, journal={Archives of Toxicology}, pages={123--143}, author={Krug, Anne-Kathrin and Kolde, Raivo and Gaspar, John A. and Rempel, Eugen and Balmer, Nina V. and Waldmann, Tanja and Kadereit, Suzanne and Hengstler, Jan G. and Rahnenführer, Jörg and Leist, Marcel and Sachinidis, Agapios} }

Krug, Anne-Kathrin eng 2014-08-14T22:25:04Z Kadereit, Suzanne Gaspar, John A. Leist, Marcel Sachinidis, Agapios Balmer, Nina V. Hengstler, Jan G. Balmer, Nina V. Rahnenführer, Jörg Rahnenführer, Jörg Developmental 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. Human embryonic stem cell-derived test systems for developmental neurotoxicity : a transcriptomics approach Rempel, Eugen Hengstler, Jan G. Leist, Marcel 2013-01 2013-09-10T12:50:59Z Sachinidis, Agapios Archives of Toxicology ; 87 (2013), 1. - S. 123-143 Rempel, Eugen Gaspar, John A. deposit-license Waldmann, Tanja Krug, Anne-Kathrin Kadereit, Suzanne Kolde, Raivo Kolde, Raivo Waldmann, Tanja

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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