LECT2 promotes liver regeneration across developmental stages by activating the ADAM10-NOTCH signaling pathway
Bibliographic record
Abstract
BACKGROUND: Liver regeneration is a highly complex biological process, and the molecular mechanisms governing regenerative capacity exhibit significant divergence across distinct developmental stages. This study aimed to developmentally conserve pro-regenerative regulators of the liver and elucidate their mechanistic roles in the developmental stages of liver regeneration. METHODS: Wild-type mice at distinct developmental stages, including 1-month-old (adolescent), 4-month-old (adult), 12-month-old (middle-aged), and 20-month-old (aged), underwent sham surgery or 2/3 partial hepatectomy. RNA sequencing and scRNA-seq identified the target gene and spatial expression. Hepatocyte proliferation was assessed by Ki-67, PCNA staining, and hematoxylin and eosin staining. Functional and mechanistic studies have employed bioinformatics, IF, coimmunoprecipitation, quantitative real-time PCR, and small-molecule inhibition. RESULTS: RNA sequencing across age groups identified leukocyte cell-derived chemotaxin 2 (LECT2) as a functionally significant mediator in liver regeneration processes. Longitudinal assessment of murine liver regeneration models and patients who underwent hepatectomy revealed dynamic LECT2 expression patterns. LECT2 expression positively correlated with regeneration markers Ki-67 and PCNA. Lect2-KO mice in 4 age groups exhibited impaired liver regeneration. Immunofluorescence staining and single-cell RNA sequencing demonstrated predominant hepatocyte-specific expression of LECT2. Hepatocyte-specific Lect2 knockout significantly impaired liver regeneration following 2/3 partial hepatectomy. Interestingly, there appeared to be no difference in the level of regeneration in mice with suppressed A Disintegrin and Metalloproteinase Domain 10 (ADAM10) expression despite Lect2 overexpression. Mechanistic investigations revealed that LECT2 potentiates hepatic regeneration by activating the ADAM10-NOTCH signaling pathway. Finally, our in vivo therapeutic model demonstrated that adeno-associated virus-mediated Lect2 overexpression significantly enhanced the posthepatectomy regenerative capacity. CONCLUSIONS: LECT2 promotes liver regeneration across developmental stages by activating the ADAM10-NOTCH signaling pathway, providing a promising therapeutic target for enhancing hepatic 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 | 0.000 | 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 | 0.001 | 0.001 |
| 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".