Abstract 155: Lin28 Enhances Cardiac Progenitor Cell Ability to Repair the Heart by Reprogramming Cellular Metabolism
Bibliographic record
Abstract
Rationale: The adult Heart is largely a dormant organ supporting limited cellular turnover. In contrast, neonatal cardiac tissue proliferates and is capable of regeneration while operating under a specialized metabolic state. During transition to adulthood, cardiac metabolism undergoes a rapid shift that coincides with termination of regenerative processes. Whether altering cardiac metabolism recapitulates regenerative potential remains untested. Recently, introduction of Lin28, a metabolic regulator of pluripotency, enhances tissue repair after injury. Nevertheless, there are no studies characterizing the effect of Lin28 on cardiac repair. Objective: Determine the effect of Lin28 on cardiac progenitor cell function and cardiac repair after injury. Methods and Results: Lin28 expression coincides during heart development with c-kit and declines postnatal with complete abrogation in 3-week-old adult heart as measured by qRT-PCR and immunohistochemistry. CPCs were engineered with Lin28-GFP (CPCLin) lentivirus GFP expressing CPCs were used as controls (CPC-G). CPCLin demonstrated increased proliferation measured by CyQuant compared to CPC-G, concurrent with decreased apoptosis. Interestingly, CPCLin demonstrated a significant increase in lactate production, pyruvate kinase activity, glucose uptake together with enhancement of glycolysis and expression of glycolytic enzymes compared to CPC-G. Oxidative metabolism was also upregulated together with increased intracellular ATP in CPCLin compared to controls. Additionally, CPCLin demonstrated significantly reduced ROS generation as measured by CM-H 2 TMROS based FACS analysis compared to CPC-G. To determine in vivo efficacy, CPCLin and CPC-G were transplanted in the heart after myocardial infarction. CPC-Lin hearts showed significant increase in cardiac structure and function 8 weeks after MI. Increased persistence and proliferation of transplanted CPC-Lin cells together with reduced apoptosis were observed in CPCLin hearts compared to control CPC-G hearts 2 days after transplantation. Conclusions: Lin28 modification of CPCs reprograms cellular metabolism in CPCs enhancing proliferation and survival including ability to repair the heart after myocardial injury.
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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 | 0.002 | 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".