High Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiation

  1. Seidel, Florian ORCID logo
  2. Cherianidou, Anna
  3. Kappenberg, Franziska ORCID logo
  4. Marta, Miriam
  5. Dreser, Nadine
  6. Blum, Jonathan ORCID logo
  7. Waldmann, Tanja
  8. Blüthgen, Nils
  9. Meisig, Johannes
  10. Madjar, Katrin
  11. Henry, Margit
  12. Rotshteyn, Tamara
  13. Scholtz-Illigens, Andreas ORCID logo
  14. Marchan, Rosemarie ORCID logo
  15. Edlund, Karolina ORCID logo
  16. Leist, Marcel ORCID logo
  17. Rahnenführer, Jörg ORCID logo
  18. SACHINIDIS, Agapios ORCID logo
  19. Hengstler, Jan ORCID logo

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1000 Titel
  • High Accuracy Classification of Developmental Toxicants by In Vitro Tests of Human Neuroepithelial and Cardiomyoblast Differentiation
1000 Autor/in
  1. Seidel, Florian |
  2. Cherianidou, Anna |
  3. Kappenberg, Franziska |
  4. Marta, Miriam |
  5. Dreser, Nadine |
  6. Blum, Jonathan |
  7. Waldmann, Tanja |
  8. Blüthgen, Nils |
  9. Meisig, Johannes |
  10. Madjar, Katrin |
  11. Henry, Margit |
  12. Rotshteyn, Tamara |
  13. Scholtz-Illigens, Andreas |
  14. Marchan, Rosemarie |
  15. Edlund, Karolina |
  16. Leist, Marcel |
  17. Rahnenführer, Jörg |
  18. SACHINIDIS, Agapios |
  19. Hengstler, Jan |
1000 Erscheinungsjahr 2022
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-10-27
1000 Erschienen in
1000 Quellenangabe
  • 11(21):3404
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/cells11213404 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653768/ |
1000 Ergänzendes Material
  • https://www.mdpi.com/2073-4409/11/21/3404#app1-cells-11-03404 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal alternative testing strategies
lokal toxicogenomics
lokal gene expression
lokal drug screening
lokal induced pluripotent stem cells
lokal transcriptomics
lokal in vitro test
lokal developmental and reproductive toxicity
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-4466-332X|https://frl.publisso.de/adhoc/uri/Q2hlcmlhbmlkb3UsIEFubmE=|https://orcid.org/0000-0001-8066-5333|https://frl.publisso.de/adhoc/uri/TWFydGEsIE1pcmlhbQ==|https://frl.publisso.de/adhoc/uri/RHJlc2VyLCBOYWRpbmU=|https://orcid.org/0000-0002-2058-0511|https://frl.publisso.de/adhoc/uri/V2FsZG1hbm4sIFRhbmph|https://frl.publisso.de/adhoc/uri/QmzDvHRoZ2VuLCBOaWxz|https://frl.publisso.de/adhoc/uri/TWVpc2lnLCBKb2hhbm5lcw==|https://frl.publisso.de/adhoc/uri/TWFkamFyLCBLYXRyaW4=|https://frl.publisso.de/adhoc/uri/SGVucnksIE1hcmdpdA==|https://frl.publisso.de/adhoc/uri/Um90c2h0ZXluLCBUYW1hcmE=|https://orcid.org/0000-0002-5177-6656|https://orcid.org/0000-0003-4414-1633|https://orcid.org/0000-0002-0276-2143|https://orcid.org/0000-0002-3778-8693|https://orcid.org/0000-0002-8947-440X|https://orcid.org/0000-0003-3054-225X|https://orcid.org/0000-0002-1427-5246
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Bundesministerium für Bildung und Forschung |
  2. Deutsche Forschungsgemeinschaft |
  3. European Chemical Industry Council |
  4. Danish Environmental Protection Agency |
  5. Land Baden-Württemberg |
  6. Horizon 2020 Framework Programme |
1000 Fördernummer
  1. 031L0117A-D
  2. 427806116
  3. -
  4. MST-667-00205
  5. NAM-ACCEPT
  6. 964537; 964518; 825759
1000 Förderprogramm
  1. Project SysDT;; RTG 2624
  2. -
  3. -
  4. -
  5. -
  6. RISK-HUNT3R; ToxFree; ENDpoiNTs
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm Project SysDT;; RTG 2624
    1000 Fördernummer 031L0117A-D
  2. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer 427806116
  3. 1000 joinedFunding-child
    1000 Förderer European Chemical Industry Council |
    1000 Förderprogramm -
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer Danish Environmental Protection Agency |
    1000 Förderprogramm -
    1000 Fördernummer MST-667-00205
  5. 1000 joinedFunding-child
    1000 Förderer Land Baden-Württemberg |
    1000 Förderprogramm -
    1000 Fördernummer NAM-ACCEPT
  6. 1000 joinedFunding-child
    1000 Förderer Horizon 2020 Framework Programme |
    1000 Förderprogramm RISK-HUNT3R; ToxFree; ENDpoiNTs
    1000 Fördernummer 964537; 964518; 825759
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6483131.rdf
1000 Erstellt am 2024-06-17T12:29:31.249+0200
1000 Erstellt von 254
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1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Tue Jun 18 08:10:19 CEST 2024
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1000 Oai Id
  1. oai:frl.publisso.de:frl:6483131 |
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