Transcriptome-based prediction of drugs, inhibiting cardiomyogenesis in human induced pluripotent stem cells.


Journal

Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035

Informations de publication

Date de publication:
29 Aug 2023
Historique:
received: 06 06 2023
accepted: 16 08 2023
revised: 31 07 2023
medline: 30 8 2023
pubmed: 30 8 2023
entrez: 29 8 2023
Statut: epublish

Résumé

Animal studies for embryotoxicity evaluation of potential therapeutics and environmental factors are complex, costly, and time-consuming. Often, studies are not of human relevance because of species differences. In the present study, we recapitulated the process of cardiomyogenesis in human induced pluripotent stem cells (hiPSCs) by modulation of the Wnt signaling pathway to identify a key cardiomyogenesis gene signature that can be applied to identify compounds and/or stress factors compromising the cardiomyogenesis process. Among the 23 tested teratogens and 16 non-teratogens, we identified three retinoids including 13-cis-retinoic acid that completely block the process of cardiomyogenesis in hiPSCs. Moreover, we have identified an early gene signature consisting of 31 genes and associated biological processes that are severely affected by the retinoids. To predict the inhibitory potential of teratogens and non-teratogens in the process of cardiomyogenesis we established the "Developmental Cardiotoxicity Index" (CDI

Identifiants

pubmed: 37644023
doi: 10.1038/s41420-023-01616-6
pii: 10.1038/s41420-023-01616-6
pmc: PMC10465524
doi:

Types de publication

Journal Article

Langues

eng

Pagination

321

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RTG 2624
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RTG 2624

Informations de copyright

© 2023. Cell Death Differentiation Association (ADMC).

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Auteurs

Anna Cherianidou (A)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany.

Franziska Kappenberg (F)

Department of Statistics, TU Dortmund University, Vogelpothsweg 87, 44227, Dortmund, Germany.

Florian Seidel (F)

Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.

Aviseka Acharya (A)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany.

Panagiota Papazoglou (P)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany.

Sureshkumar Perumal Srinivasan (SP)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany.

Jürgen Hescheler (J)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany.

Luying Peng (L)

Heart Health Center, Shanghai East Hospital, School of Medicine, Tongji University, 200120, Shanghai and Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, 100730, Beijing, China.

Marcel Leist (M)

In Vitro Toxicology and Biomedicine, Department of Biology, University of Konstanz, Universitätsstr. 10, PO, Box M657, 78457, Constance, Germany.

Jan G Hengstler (JG)

Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.

Jörg Rahnenführer (J)

Department of Statistics, TU Dortmund University, Vogelpothsweg 87, 44227, Dortmund, Germany.

Agapios Sachinidis (A)

University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Physiology, Working Group Sachinidis, 50931 Cologne, Germany Robert-Koch-Str. 39, 50931, Cologne, Germany. a.sachinidis@uni-koeln.de.

Classifications MeSH