ArticleCell reports2021
Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Contractility Drives Cardiomyocyte Maturation and the Response to Nanopatterns.Circulation research · 2026Article
- Titin cleavage in living cardiomyocytes induces sarcomere disassembly but does not trigger cell proliferation.The Journal of biological chemistry · 2026Article
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.Stem cell reports · 2025Article
- Engineered Cardiac Tissues as a Platform for CRISPR-Based Mitogen Discovery.Advanced healthcare materials · 2025Article
- Transition from fetal to postnatal state in the heart: Crosstalk between metabolism and regeneration.Development, growth & differentiation · 2024Review
- Noncontractile Stem Cell-Cardiomyocytes Preserve Post-Infarction Heart Function.Circulation research · 2024Article
- Polyploidy in Cancer: Causal Mechanisms, Cancer-Specific Consequences, and Emerging Treatments.Molecular cancer therapeutics · 2024Review
- Article
- Vascularization of PEGylated fibrin hydrogels increases the proliferation of human iPSC-cardiomyocytes.Journal of biomedical materials research. Part A · 2024Article
- Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2023Review
- Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering.Circulation research · 2023Review
- CRISPR screening in cardiovascular research.Frontiers in cell and developmental biology · 2023Review
- The Cardiac Sarcomere and Cell Cycle.Current cardiology reports · 2022Review
- Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure.Circulation · 2022Article
- Metabolic Regulation of Cardiac Regeneration.Frontiers in cardiovascular medicine · 2022Review
- The Role of Metabolism in Heart Failure and Regeneration.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.