RT Journal Article
T1 Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation
A1 Aix, Esther
A1 Gutiérrez-Gutiérrez, Óscar
A1 Sánchez-Ferrer, Carlota
A1 Aguado Sánchez, Tania
A1 Flores, Ignacio
AB The molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc−/−) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc−/− newborns but rescued in G3 Terc−/−/p21−/− mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts.
PB Rockefeller University Press
SN 0021-9525
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/91537
UL https://hdl.handle.net/20.500.14352/91537
LA eng
NO Esther Aix, Óscar Gutiérrez-Gutiérrez, Carlota Sánchez-Ferrer, Tania Aguado, Ignacio Flores; Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation. J Cell Biol 6 June 2016; 213 (5): 571–583. doi: https://doi.org/10.1083/jcb.201510091
NO Ministerio de Economía, Industria y Competitividad (España)
NO Fundación Científica Asociación Española Contra el Cáncer
DS Docta Complutense
RD 11 abr 2025