Abstract 414: Postnatal Cardiac Tissue Harbors Progenitor Cells With Unique Metabolic Profile
Bibliographic record
Abstract
Rationale: The developmental cardiac tissue is a proliferative organ capable of regeneration that extends briefly into the postnatal period. Studies show that the heart undergoes alterations in metabolism that coincide with cessation of regenerative processes during postnatal development. Whether cardiac cells in the early postnatal heart exhibit metabolic properties that favor regeneration remains unknown. Objective: To determine whether postnatal cardiac tissue harbors CPCs with unique metabolic profile. Methods and Results: CPCs were isolated from C57BL/6 mice aged 2-day (NCPC), 2-month (adult CPC) and 2-year old (ACPC). Morphological assessment showed NCPCs were smaller and rounded compared to CPCs and ACPCs and expressed putative stem cell markers and were negative for hematopoietic marker CD45. Interestingly, NCPCs expressed elevated levels of pluripotency markers such as LIN28 compared to ACPCs and CPCs. Increased viability, proliferation rate, metabolic activity and reduced doubling times were observed in NCPCs compared to CPCs and ACPCs measured by CyQuant, MTT, and Resazurin assays. NCPCs demonstrated a youthful phenotype and were resistant to H2O2 induced stress compared to ACPCs and CPCs as measured by β-Galactosidase and TUNEL labeling respectively together with a unique expression of paracrine factors as assessed by proteome profiler array. Interestingly, NCPCs demonstrated increased ATP generation, glycolytic activity and reduced oxidative phosphorylation compared to CPCs and ACPCs measured by seahorse assay parallel with enhanced expression of glycolytic enzymes measured by qRT-PCR and western blot. NCPCs showed increased lactate production and pyruvate kinase activity and low mitochondrial membrane potential. Interestingly, mitochondrial fuel dependency assay showed increased glutamine dependency as the fuel for mitochondrial oxidative phosphorylation. RNA-sequencing analysis demonstrated increased expression of metabolic signaling in NCPCs compared to CPCs and ACPCs. Conclusions: Postnatal cardiac tissue possesses progenitor cell population with unique metabolic profile that coincides with enhanced functional properties of NCPCs suggesting their potential therapeutic value for cardiac repair.
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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 | 0.001 | 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 | 0.001 |
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".