Increased proliferation of hepatic periportal ductal progenitor cells contributes to persistent hypermetabolism after trauma
Bibliographic record
Abstract
Abstract Prolonged and persistent hypermetabolism and excessive inflammatory response after severe trauma is detrimental and associated with poor outcome. The predisposing pathology or signals mediating this complex response are essentially unknown. As the liver is the central organ mediating the systemic metabolic responses and considering that adult hepatic stem cells are on top of the hierarchy of cell differentiation and may pass epigenetic information to their progeny, we asked whether liver progenitor cells are activated, signal hypermetabolism upon post‐traumatic cellular stress responses, and pass this to differentiated progeny. We generated Sox9CreER T2 : ROSA26 EYFP mice to lineage‐trace the periportal ductal progenitor cells (PDPCs) and verify the fate of these cells post‐burn. We observed increased proliferation of PDPCs and their progeny peaking around two weeks post‐burn, concomitant with the hepatomegaly and the cellular stress responses. We then sorted out PDPCs, PDPC‐derived hepatocytes and mature hepatocytes, compared their transcriptome and showed that PDPCs and their progeny present a significant up‐regulation in signalling pathways associated with inflammation and metabolic activation, contributing to persistent hypermetabolic and hyper‐inflammatory state. Furthermore, concomitant down‐regulation of LXR signalling in PDPCs and their progeny implicates the therapeutic potential of early and short‐term administration of LXR agonists in ameliorating such persistent hypermetabolism.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".