Nestin <sup>(+)</sup> ‐ and Nestin <sup>(−)</sup> ‐Ventricular Cardiomyocytes Reenter the Cell Cycle In Vitro but Are Reciprocally Regulated in the Partial Apex‐Resected 7‐Day Neonatal Rat Heart
Bibliographic record
Abstract
ABSTRACT The 1‐day‐old neonatal rat heart contains two subpopulations of ventricular cardiomyocytes (NNVMs) that reenter the cell cycle in vitro and in vivo distinguished by the absence or de novo expression of the intermediate filament protein nestin. Furthermore, de novo nestin expression in NNVMs directly facilitated cell cycle reentry and elicited a morphological migratory phenotype. Previous studies have reported that ventricular cardiomyocytes failed to reenter the cell cycle following damage to the 7‐day‐old rodent heart. The present study tested the hypothesis that cell cycle reentry of one or both of the NNVM subpopulations of 7‐day‐old neonatal rat pups was compromised in vitro and/or in vivo following cardiac damage. Three‐day treatment of 7‐day‐old NNVMs with the protein kinase C activator phorbol 12,13‐dibutyrate and the serine/threonine p38α/β MAPK kinase inhibitor SB203580 facilitated cell cycle reentry into the S phase and G 2 –M phase of the cell cycle. Two distinct subpopulations of 7‐day NNVMs reentered the cell cycle, and the predominant subpopulation was distinguished by de novo nestin expression. Three days following the sham‐operation of 7‐day‐old neonatal rat hearts, cell cycle reentry was detected exclusively in NNVMs lacking nestin expression. Partial apex resection of 7‐day‐old neonatal rat hearts led to the de novo appearance of nestin (+) ‐NNVMs preferentially bordering the damaged region and a subpopulation reentered the S‐phase and G 2 –M phase of the cell cycle in the absence of p38α/β MAPK inhibition. By contrast, cell cycle reentry of nestin (−) ‐NNVMs identified adjacent to the apex‐resected region was significantly reduced. These data highlight the disparate in vivo regulation of the two subpopulations of NNVMs following damaged to the 7‐day‐old neonatal rat heart and reaffirm the premise that targeting the subpopulation of nestin (+) ‐ventricular cardiomyocytes identified in the ischemically damaged adult mammalian heart represents a plausible first step to initiate cell cycle reentry.
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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".