Universität zu Köln

Seidel, Florian, Cherianidou, Anna, Kappenberg, Franziska ORCID: 0000-0001-8066-5333, Marta, Miriam, Dreser, Nadine, Blum, Jonathan ORCID: 0000-0002-2058-0511, Waldmann, Tanja, Bluthgen, Nils, Meisig, Johannes, Madjar, Katrin ORCID: 0000-0001-6169-8105, Henry, Margit, Rotshteyn, Tamara, Scholtz-Illigens, Andreas, Marchan, Rosemarie, Edlund, Karolina, Leist, Marcel ORCID: 0000-0002-3778-8693, Rahnenfuehrer, Joerg, Sachinidis, Agapios and Hengstler, Jan Georg (2022). High Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiation. Cells, 11 (21). BASEL: MDPI. ISSN 2073-4409

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Abstract

Human-relevant tests to predict developmental toxicity are urgently needed. A currently intensively studied approach makes use of differentiating human stem cells to measure chemically-induced deviations of the normal developmental program, as in a recent study based on cardiac differentiation (UKK2). Here, we (i) tested the performance of an assay modeling neuroepithelial differentiation (UKN1), and (ii) explored the benefit of combining assays (UKN1 and UKK2) that model different germ layers. Substance-induced cytotoxicity and genome-wide expression profiles of 23 teratogens and 16 non-teratogens at human-relevant concentrations were generated and used for statistical classification, resulting in accuracies of the UKN1 assay of 87-90%. A comparison to the UKK2 assay (accuracies of 90-92%) showed, in general, a high congruence in compound classification that may be explained by the fact that there was a high overlap of signaling pathways. Finally, the combination of both assays improved the prediction compared to each test alone, and reached accuracies of 92-95%. Although some compounds were misclassified by the individual tests, we conclude that UKN1 and UKK2 can be used for a reliable detection of teratogens in vitro, and that a combined analysis of tests that differentiate hiPSCs into different germ layers and cell types can even further improve the prediction of developmental toxicants.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seidel, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Cherianidou, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Kappenberg, Franziska UNSPECIFIED orcid.org/0000-0001-8066-5333 UNSPECIFIED Marta, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreser, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Blum, Jonathan UNSPECIFIED orcid.org/0000-0002-2058-0511 UNSPECIFIED Waldmann, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluthgen, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Meisig, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Madjar, Katrin UNSPECIFIED orcid.org/0000-0001-6169-8105 UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotshteyn, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholtz-Illigens, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Marchan, Rosemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED Edlund, Karolina UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED Rahnenfuehrer, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Hengstler, Jan Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687098
DOI:	10.3390/cells11213404
Journal or Publication Title:	Cells
Volume:	11
Number:	21
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLURIPOTENT STEM-CELLS; GENE-EXPRESSION DATA; TRANSCRIPTOME RESPONSES; TOXICITY; NEUROTOXICITY; BIOMARKERS; FETAL Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68709