Regulation of cardiac fibroblast population and cell fate by Scleraxis (15.2)
Bibliographic record
Abstract
Fibroblasts are cells of mesenchymal origin that constitute majority of the cardiac non‐myocyte population. They play a contributory role in development and structure of the myocardium, cellular signaling and electromechanical function of the heart‐ both in healthy and diseased conditions. Scleraxis (Scx) has been demonstrated to play a vital role in human collagen gene regulation and synthesis of extracellular matrix (ECM) components. Genetic ablation of Scx caused marked changes in the matrix composition of hearts of Scx null (KO) mice. Based on these observations, we hypothesized that the overall changes occurring in the myocardium may be due to a net change in population of the contributory synthetic fibroblasts. Using single‐cell suspensions from Scx KO and wildtype (WT) hearts, flow cytometry analysis was performed. There was a significant reduction (>40%) in DDR2 positive fibroblasts in Scx KO hearts compared to WT samples. There was also a trending decrease in the population of cells that stained positive for α‐smooth muscle actin (αSMA), a marker of activated contractile myofibroblast phenotype. Gene and protein expression analyses of fibroblast/ myofibroblast markers (vimentin, periostin, EDA‐fibronectin, SMemb) exhibited an overall downregulation of these proteins in myocardium devoid of Scx‐ thus suggesting involvement of Scx in fibroblast cell fate regulation. We hypothesized that Scx may also be responsible for modulating the process of fibroblast phenoconversion‐ a phenomenon that is known to accompany cardiac remodeling. qPCR and immunoblotting analyses of Scx KO hearts demonstrated a significant downregulation of αSMA expression. shRNA‐mediated knockdown of Scx gene expression in primary cardiac proto‐myofibroblasts resulted in marked diminution of this myofibroblast marker protein, thereby demonstrating a direct role of Scx in fibroblast phenoconversion. These findings identify Scx as a novel regulator of cardiac fibroblast population and cell fate. Grant Funding Source : Supported by the Canadian Institutes of Health Research and St. Boniface Research Foundatio
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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 | 0.000 |
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".