Multi-omic analysis reveals VEGFR2, PI3K, and JNK mediate the small molecule induction of human iPSC-derived cardiomyocyte proliferation.

ABSTRACT: Mammalian hearts lose their regenerative potential shortly after birth. Stimulating the proliferation of preexisting cardiomyocytes is a potential therapeutic strategy for cardiac damage. In a previous study, we identified 30 compounds that induced the bona-fide proliferation of human iPSC-derived cardiomyocytes (hiPSC-CM). Here, we selected five active compounds with diverse targets, including ALK5 and CB1R, and performed multi-omic analyses to identify common mechanisms mediating the cell cycle progression of hiPSC-CM. Transcriptome profiling revealed the top enriched pathways for all compounds including cell cycle, DNA repair, and kinesin pathways. Functional proteomic arrays found that the compounds collectively activated multiple receptor tyrosine kinases including ErbB2, IGF1R, and V

SUBMITTER: Woo LA 

PROVIDER: S-EPMC11338145 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature