2026-07-21T14:19:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52212024-09-27T09:07:58Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Aix, Esther
author
Gutierrez-Gutierrez, Oscar
author
Sanchez-Ferrer, Carlota
author
Aguado, Tania
author
Flores, Ignacio
funder
Ministerio de Educación (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Asociación Española Contra el Cáncer
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2017-10-30T13:15:44Z
2017-10-30T13:15:44Z
2016
J Cell Biol. 2016; 213(5):571-83
10.1083/jcb.201510091
1540-8140
0021-9525
Journal of Cell Biology
27241915
http://hdl.handle.net/20.500.12105/5221
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.
eng
MOUSE HEART
TERMINAL TRANSFERASE
CARDIAC REGENERATION
OXIDATIVE STRESS
MAMMALIAN HEART
STEM-CELLS
PROLIFERATION
EXPRESSION
CANCER
MICE
Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation
journal article
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PostnatalTelomereDysfunctionInduces_2016
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PostnatalTelomereDysfunctionInduces_2016_Supp
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PostnatalTelomereDysfunctionInduces_2016.txt
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PostnatalTelomereDysfunctionInduces_2016_Supp.txt