Abstract 347: Identification and Characterization of a miRNA Cohort Initiated Transitional Program That Controls Cell Cycle Arrest of the Perinatal Heart
Bibliographic record
Abstract
During fetal and early perinatal development the myocardium undergoes a period of hyperplastic growth, which results in an exponential increase in the number of cardiomyocytes (CM) that will constitute the adult heart. Soon after birth, CMs proceed through a final round of cell division in the absence cytokinesis that results in binucleation of >95% of adult CMs. Fetal heart genes are re-activated with the onset of pathological hypertrophic or dilated cardiomyopathies, yet there is no evidence of CM re-entry into the cell cycle. Despite the importance of this phenomenon, little is known about the molecular basis for the transition from hyperplastic to hypertrophic-based myocardial growth. Hypothesis: A perinatal heart gene program is necessary for the normal transition from a fetal heart gene program to an adult heart gene program. To identify the molecular mechanisms and pathways involved in CM differentiation during the perinatal transition, RNA was isolated from E18, and 1, 3, 5, 7, 10 and 35d old mouse hearts. CM gene expression and micro-RNA profiles (n=3 arrays/time point) were determined by oligonucleotide array analysis. The raw array data was normalized by Robust Multi-array analysis. Empirical Bayes estimation of gene-specific variances was performed between each of the time points in order to identify genes that are transiently and significantly changed at days 3 and 5 as compare to E18 and 10d post-birth. The analysis identified 2,799 genes (E18 v 5d) and 3,347 genes (5d v 10d) that were then clustered to determine significant pathway enrichment (p<0.05) with Ingenuity Pathway Analysis. Our analysis confirmed previous observations of a down regulation of glucose oxidative metabolism (p=0.02) with an up-regulation of fatty acid metabolism (p=0.0001) between E18 and 5d post-birth. Also, 63 cell cycle genes are collectively down regulated (p=4.3x10-4) between 5d and 10d post-birth. We identified 131 genes that are transiently up regulated at 5d compared to E18 and 10d and this transition was proceeded by a specific cohort of miRNAs. The data generated from this study provide new insight into the molecular mechanisms by which CMs regulate and permanently exit from the cell cycle.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".