Universität zu Köln

Colleoni, Silvia, Galli, Cesare, Gaspar, John Antony, Meganathan, Kesavan, Jagtap, Smita, Hescheler, Jurgen, Zagoura, Dimitra, Bremer, Susanne, Sachinidis, Agapios and Lazzari, Giovanna (2014). A comparative transcriptomic study on the effects of valproic acid on two different hESCs lines in a neural teratogenicity test system. Toxicol. Lett., 231 (1). S. 38 - 45. CLARE: ELSEVIER IRELAND LTD. ISSN 1879-3169

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Abstract

A number of in vitro toxicity assays based on human embryonic stem cells (hESCs) are under development in order to provide alternative methods for the screening of chemicals and drugs and to reduce the number of animals needed for developmental toxicity assessment. The major challenge is to demonstrate the reliability of these in vitro methods by correlating the in vitro produced results to the available in vivo data. In this context transcriptomic approaches associated to toxicogenomic database analysis give the possibility to screen, annotate and cluster high numbers of genes and to identify the molecular changes that univocally mark the toxicity induced processes or are indicative of the early initiating events that lead to cellular toxicity. In this retrospective study we compare microarray transcriptomic data derived from two different hESCs lines (HUES1 and H9) exposed to valproic acid (VA) while applying the same differentiation protocol. We present the results of this comparative analysis in light of the known teratogenic effects of VA. The results show molecular changes in the processes of neural development, neural crest migration, apoptosis and regulation of transcription, indicating a good correspondence with the available in vivo data. We also describe common toxicological signatures and provide an interpretation of the observed qualitative differences referring to known biological features of the two hESCs lines. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Colleoni, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Galli, Cesare UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaspar, John Antony UNSPECIFIED UNSPECIFIED UNSPECIFIED Meganathan, Kesavan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jagtap, Smita UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Zagoura, Dimitra UNSPECIFIED UNSPECIFIED UNSPECIFIED Bremer, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Lazzari, Giovanna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423165
DOI:	10.1016/j.toxlet.2014.08.023
Journal or Publication Title:	Toxicol. Lett.
Volume:	231
Number:	1
Page Range:	S. 38 - 45
Date:	2014
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1879-3169
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EMBRYONIC STEM-CELLS; IN-VITRO; NERVOUS-SYSTEM; TUBE DEFECTS; EXPRESSION; CREST; GENE; EXPOSURE; BLASTOCYSTS; DERIVATION Multiple languages Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42316