Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells
| العنوان: | Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells |
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| المؤلفون: | Paul Jennings, Giada Carta, Pranika Singh, Daniel da Costa Pereira, Anita Feher, Andras Dinnyes, Thomas E. Exner, Anja Wilmes |
| المساهمون: | Molecular and Computational Toxicology, AIMMS |
| المصدر: | Jennings, P, Jennings, P, Singh, P, da Costa Pereira, D, Feher, A, Dinnyes, A, Exner, T E & Wilmes, A 2022, ' Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells ', Cell biology and toxicology . https://doi.org/10.1007/s10565-022-09783-5 Cell biology and toxicology. Springer Netherlands |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Health, Toxicology and Mutagenesis, Cell Biology, Toxicology |
| الوصف: | Transcriptomic analysis is a powerful method in the utilization of New Approach Methods (NAMs) for identifying mechanisms of toxicity and application to hazard characterization. With this regard, mapping toxicological events to time of exposure would be helpful to characterize early events. Here, we investigated time-dependent changes in gene expression levels in iPSC-derived renal proximal tubular-like cells (PTL) treated with five diverse compounds using TempO-Seq transcriptomics with the aims to evaluate the application of PTL for toxicity prediction and to report on temporal effects for the activation of cellular stress response pathways. PTL were treated with either 50 μM amiodarone, 10 μM sodium arsenate, 5 nM rotenone, or 300 nM tunicamycin over a temporal time course between 1 and 24 h. The TGFβ-type I receptor kinase inhibitor GW788388 (1 μM) was used as a negative control. Pathway analysis revealed the induction of key stress-response pathways, including Nrf2 oxidative stress response, unfolding protein response, and metal stress response. Early response genes per pathway were identified much earlier than 24 h and included HMOX1, ATF3, DDIT3, and several MT1 isotypes. GW788388 did not induce any genes within the stress response pathways above, but showed deregulation of genes involved in TGFβ inhibition, including downregulation of CYP24A1 and SERPINE1 and upregulation of WT1. This study highlights the application of iPSC-derived renal cells for prediction of cellular toxicity and sheds new light on the temporal and early effects of key genes that are involved in cellular stress response pathways. |
| تدمد: | 1573-6822 0742-2091 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7626ff9d6b35df57d0acbec77d2cc02a https://pubmed.ncbi.nlm.nih.gov/36586010 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7626ff9d6b35df57d0acbec77d2cc02a |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15736822 07422091 |
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