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CRISPR screening using Human PSC-derived cardiomyocytes reveals TAOK1 as a potential therapeutic target for doxorubicin-induced cardiomyopathy I

GSE255504 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/02/08 Platform GPL24676
Summary
Doxorubicin (DOX) is one of the most effective chemotherapeutic agents for various types of cancers. However, DOX often causes cardiotoxicity referred to as DOX-induced cardiomyopathy (DIC). Despite extensive research aimed at identifying therapeutic targets for DIC, only a limited number of effective treatments are available. In this study, we identified a member of the STE20 kinase family, thousand and one amino acid protein kinase 1 (TAOK1) as a potential regulator for DOX-induced cardiomyocyte death using a kinome-wide CRISPR gene knockout screen in human cardiomyocytes derived from pluripotent stem cells (hPSC-CMs). TAOK1 suppression improved DOX-induced cardiomyocyte dysfunction in hPSC-CMs and rescued cardiac function in a DIC mouse model. Mechanistically, we found that TAOK1 regulated p38 MAPK-mediated cardiomyocyte apoptosis induced by DOX. Our results indicate TAOK1 as a promising therapeutic strategy for treating DIC in cancer patients, and highlight the advantage of hPSC-CMs as a platform to study drug-induced cardiotoxicity.
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Direct links to NCBI, no account and no request form: the whole study as GSE255504_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1075126 and SRA study SRP489183. Searching any of these in the dataset finder brings you back here.

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