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Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures

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.

Publication metadata

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


DOI: 10.1016/j.tiv.2024.105826

PubMed id: 38615723


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Funder referenceFunder name
European Union Horizon 2020