Universität zu Köln

Shinde, Vaibhav, Srinivasan, Sureshkumar Perumal, Henry, Margit, Rotshteyn, Tamara, Hescheler, Juergen, Rahnenfuehrer, Joerg, Grinberg, Marianna, Meisig, Johannes, Bluethgen, Nils, Waldmann, Tanja, Leist, Marcel ORCID: 0000-0002-3778-8693, Hengstler, Jan Georg and Sachinidis, Agapios (2016). Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells. Stem Cell Res. Ther., 7. LONDON: BMC. ISSN 1757-6512

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Abstract

Background: Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. Methods: Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools. Results: The transcriptomes on day 14 showed that more than 70% of the developmental genes (regulated genes with > 2-fold change on day 14 compared to day 0) exhibited variability among cell lines. The developmental genes belonging to all three cell lines captured biological processes and KEGG pathways related to all three germ layer embryonic development. In addition, transcriptome profiles were obtained after 14 days of exposure to teratogenic valproic acid (VPA) during differentiation. Although the differentially regulated genes between treated and untreated samples showed more than 90% variability among cell lines, VPA clearly antagonized the expression of developmental genes in all cell lines: suppressing upregulated developmental genes, while inducing downregulated ones. To quantify VPA-disturbed development based on developmental genes, we estimated the developmental potency (D-p) and developmental index (D-i). Conclusions: Despite differences in genes deregulated by VPA, uniform D-i values were obtained for all three cell lines. Given that the D-i values for VPA were similar for hESCs and hiPSCs, D-i can be used for robust hazard identification, irrespective of whether hESCs or hiPSCs are used in the test systems.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shinde, Vaibhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Srinivasan, Sureshkumar Perumal UNSPECIFIED UNSPECIFIED UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotshteyn, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahnenfuehrer, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Grinberg, Marianna UNSPECIFIED UNSPECIFIED UNSPECIFIED Meisig, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluethgen, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldmann, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED Hengstler, Jan Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-252204
DOI:	10.1186/s13287-016-0449-2
Journal or Publication Title:	Stem Cell Res. Ther.
Volume:	7
Date:	2016
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1757-6512
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HISTONE DEACETYLASE INHIBITORS; IN-VITRO; TEST SYSTEMS; PREGNANCY; VALPROATE; TOXICANTS; FUTURE; MODEL; HAIR Multiple languages Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25220