biostudies-literatureUnknown12Meng FHuman induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used to identify potential factors capable of inducing endogenous cardiomyocyte proliferation to regenerate the injured heart. L-type calcium channel blockers have previously been identified as a class of factors capable of inducing matured hiPSC-CMs to proliferate. However, the mechanism by which L-type calcium channel blockers promote hiPSC-CM proliferation remains unclear. Here we provide evidence that matured hiPSC-CMs possess plasticity to undergo dematuration in response to certain pharmacological compounds. Consistent with primary cardiomyocyte maturation during perinatal development, we found that centrosome disassembly occurs in hiPSC-CMs during plate-based, temporal, maturation. A small molecuJournal of molecular and cellular cardiology plus100295https://www.ebi.ac.uk/biostudies/studies/S-EPMC12008595biostudies-literatureMatured hiPSC-derived cardiomyocytes possess dematuration plasticity.PMC12008595Bjerre FAPoon ENKwok MHidalgo-Gonzalez AZebrowski DCMeng FAndersen DCWang QDSpater DHui YCWei RAndersson HWalentinsson AfalseMatured hiPSC-derived cardiomyocytes possess dematuration plasticity.Human induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used to identify potential factors capable of inducing endogenous cardiomyocyte proliferation to regenerate the injured heart. L-type calcium channel blockers have previously been identified as a class of factors capable of inducing matured hiPSC-CMs to proliferate. However, the mechanism by which L-type calcium channel blockers promote hiPSC-CM proliferation remains unclear. Here we provide evidence that matured hiPSC-CMs possess plasticity to undergo dematuration in response to certain pharmacological compounds. Consistent with primary cardiomyocyte maturation during perinatal development, we found that centrosome disassembly occurs in hiPSC-CMs during plate-based, temporal, maturation. A small molecu2025-01-01T00:00:00Z2025 Jun2026-05-02T14:22:37.141Z2025-07-03T03:05:17.267ZS-EPMC120085954025562810.1016/j.jmccpl.2025.100295