Cdk1 Deficiency Extends the Postnatal Window of Cardiomyocyte Proliferation and Restores Cardiac Function after Myocardial Infarction
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".