Abstract P409: GSK-3β Deficiency In Cardiomyocyte Induces Cardiac Progenitor Cell Proliferation In The Ischemic Heart
Bibliographic record
Abstract
The cardiomyocytes are terminally differentiated cells and ischemia-induced cardiomyopathy is an irreparable loss. Novel strategies are needed to induce resident cardiac progenitor cells (CPCs) proliferation in situ to enhance the possibility of cardiac regeneration. Here we sought to identify a potential role for glycogen synthase kinase-3β (GSK-3β), a critical regulator of cell proliferation and differentiation, in CPCs proliferation in the ischemic heart. Cardiomyocyte-specific conditional GSK-3β knockout (cKO) and littermate control mice were recruited and challenged with myocardial infarction (MI). The cardiac function was assessed using trans-thoracic M-mode echocardiography. The level of CPC proliferation in the ischemic cKO hearts was determined at 2, 4 and 8 weeks post-MI through immunofluorescence labeling of stem cell marker c-Kit. To confirm the lineage of identified c-Kit -positive cells (KPCs) in the heart, a hematopoietic lineage marker was stained along with c-Kit. The cardiac left ventricular chamber dimension (LVID) and contractile functions were comparable until 2 weeks post-MI. The cKO mice displayed significantly preserved LV chamber [LVIDd(mm); 5.01±0.67 vs.6.09±0.65, p =0.01] and contractile function [LVEF(%); 31.98±8.52 vs. 18.06±7.11., p =0.01] in comparison to control mice at 4 week post-MI. Consistent with protective phenotypes, an increased percentage of KPC was observed in the cKO hearts at 4 and 6-weeks post-MI which was accompanied by an increased level of cardiomyocyte proliferation. Further analysis revealed that the observed increased number of KPCs in the ischemic cKO hearts were mostly from a cardiac lineage as the majority of identified KPCs were negative for the hematopoietic marker, CD45. In conclusion, our findings strongly suggest that GSK-3β inhibits CPCc proliferation post-ischemia, and loss of GSK-3β in cardiomyocytes promotes resident CPCc proliferation potentially through paracrine mechanisms.
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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 | 0.001 |
| 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) | 0.000 | 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".