{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:36:36Z","timestamp":1787225796617,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institute of Health Research to Phyllis Billia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cyclin-dependent kinase 1 (Cdk1) is a master regulator of the G2-M transition between DNA replication and cell division. This study investigates the regulation of cardiomyocyte (CM) proliferation during the early neonatal period and following ischemic injury in adult mice. We analyzed cell cycle dynamics with the assessment of DNA synthesis, and cytokinesis in murine hearts during the first 15 days after birth. A distinct proliferative block was observed at 1 day, followed by a second wave of DNA synthesis at 4 days, leading to CM binucleation (CMBN) by day 5. Genome-wide mRNA profiling revealed the differential expression of cell cycle regulatory genes during this period, with a downregulation of factors involved in cell division and mitosis. The loss of Cdk1 impaired CMBN but extended the neonatal CM proliferation window until day 10 post-birth. In adult hearts, the cardiac-specific ablation of Cdk1 triggered CM proliferation post-myocardial-infarction (MI) in specific zones, driven by the activation of EGFR1 signaling and suppression of the anti-proliferative p38 and p53 signaling. This was accompanied by restoration of fractional shortening, mitochondrial function, and decreased reactive oxygen species. Additionally, cardiac hypertrophy was mitigated, and survival rates post-MI were increased in Cdk1-knockout mice. These findings reveal a novel role of Cdk1 in regulating cell cycle exit and re-entry in differentiated CMs and offer insights into potential strategies for cardiac repair.<\/jats:p>","DOI":"10.3390\/ijms251910824","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T06:30:03Z","timestamp":1728455403000},"page":"10824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cdk1 Deficiency Extends the Postnatal Window of Cardiomyocyte Proliferation and Restores Cardiac Function after Myocardial Infarction"],"prefix":"10.3390","volume":"25","author":[{"given":"Donya","family":"Mahiny","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute, 100 College St., Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Hauck","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, 100 College St., Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny","family":"Premsingh","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, 100 College St., Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grothe","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, 100 College St., Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-1215","authenticated-orcid":false,"given":"Filio","family":"Billia","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, 100 College St., Toronto, ON M5G 1L7, Canada"},{"name":"Division of Cardiology, University Health Network (UHN), 200 Elizabeth St., Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ijcard.2015.10.172","article-title":"The medical and socioeconomic burden of heart failure: A comparative delineation with cancer","volume":"203","author":"Farmakis","year":"2016","journal-title":"Int. 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