RNAseq time course for mature hiPS-CMs induced to proliferate with 4 cell cycle factors

The regenerative capacity of the heart after myocardial infarction (MI) is limited. Our previous study showed that ectopic introduction of Cdk1/CyclinB1 and Cdk4/CyclinD1 complexes (4F) promotes cardiomyocyte proliferation in 15-20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after MI. Here, we aim to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Temporal bulk RNAseq of mature hiPS-CMs treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in cardiomyocytes after 48 h post-infection with 4F, which was associated with sarcomere disassembly and metabolic reprogramming. Overall design: we conducted temporal bulk RNAseq on 60-day-old mature hiPS-CMs infected with either LacZ (control) or CDK1, CDK4, CCNB, CCND (4F) adenovirus for 24, 48 or 72 h.