Increasing Mononuclear Diploid Cardiomyocytes by Loss of E2F Transcription Factor 7/8 Fails to Improve Cardiac Regeneration After Infarct
Zhe Yu, Lunfeng Zhang, Paola Cattaneo, Nuno Guimarães‐Camboa, Xi Fang, Yusu Gu, Kirk L. Peterson, Julius Bogomolovas, Cecilia Cuitino, Gustavo Leone, Ju Chen, Sylvia Μ. Evans
Abstract
he heart is among the least regenerative of organs. Transition of cardiomyocytes (CMs) from hyperplasic to hypertrophic growth occurs after birth, accompanied by binucleation and polyploidization, suggested as a barrier to cardiac regeneration. Cardiac regeneration and functional recovery after myocardial infarction (MI) have been correlated with an increased baseline frequency of mononuclear diploid (MND) CMs. 1 However, the capacity of MND adult CMs to undergo proliferation is still controversial. RNA-sequencing analyses of fluorescence-activated cell sorting-separated CMs suggested transcriptional differences between mononuclear and binuclear CMs, 2 yet other studies using scRNA-sequencing 3 or bulk RNA-sequencing 4 analyses found similar transcriptomes between mononuclear and multinuclear CMs in both normal and postinjury conditions. Our aim was to further investigate the regenerative potential of MND CMs.