Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Pettinato, Anthony M. et al.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies.

iDeal ChIP-seq Kit for Transcription Factors

Share this article

May, 2021


Products used in this publication

  • cut and tag antibody icon
    H3K27ac Antibody
  • cut and tag antibody icon
    H3K4me1 Antibody
  • cut and tag antibody icon
    H3K4me3 Antibody
  • cut and tag antibody icon
    H3K27me3 Antibody
  • cut and tag antibody icon
    H3K9me3 Antibody
  • ChIP-seq Grade
    H3K36me3 Antibody
  • ChIP kit icon
    iDeal ChIP-seq kit for Transcription Factors


  • EpiPlant 2024
    Clermont-Ferrand, France
    Jul 10-Jul 12, 2024
 See all events


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy