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Lookup NU author(s): Ivo Djidrovski, Professor Lyle Armstrong
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors. Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells. A targeted transcriptomic approach was employed to understand the effects of differentiation protocols on these cell types. Pearson correlation and principal component analysis (PCA) separated most of the intended target cell types and undifferentiated iPSC models as distinct groups with a high correlation among replicates from the same model. Based on PCA, the intended target cell types could also be separated into the three germ layer groups (ectoderm, endoderm and mesoderm). Differential expression analysis (DESeq2) presented the upregulated genes in each intended target cell types that allowed the evaluation of the differentiation to certain degree and the selection of key differentiation markers. In conclusion, these data confirm the versatile use of iPSC differentiated cell types as standardizable and relevant model systems for in vitro toxicology.
Author(s): Chandrasekaran V, Wellens S, Bourguignon A, Djidrovski I, Fransen L, Ghosh S, Mazidi Z, Murphy C, Nunes C, Singh P, Zana M, Armstrong L, Dinnyes A, Grillari J, Grillari-Voglauer R, Leonard MO, Verfaillie C, Wilmes A, Zurich M-G, Exner T, Jennings P, Culot M
Publication type: Article
Publication status: Published
Journal: Toxicology in Vitro
Year: 2024
Volume: 98
Print publication date: 01/06/2024
Online publication date: 12/04/2024
Acceptance date: 09/04/2024
Date deposited: 15/05/2024
ISSN (print): 0887-2333
ISSN (electronic): 1879-3177
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.tiv.2024.105826
DOI: 10.1016/j.tiv.2024.105826
PubMed id: 38615723
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