Loss of <i>Regulator of telomere elongation helicase (Rtel1)</i> impairs alveolar epithelial cell progenitor function but does not exacerbate experimental fibrosis
Bibliographic record
Abstract
Abstract Inherited loss-of-function mutations in the replication-associated helicase Regulator of telomere elongation helicase ( RTEL1 ) are among the most frequent monogenic causes of familial pulmonary fibrosis (FPF), but the specific functional role of RTEL1 in lung development, homeostasis, and injury-repair has not been determined. Using single-cell RNA-sequencing to define the cellular diversity and molecular programs following intratracheal bleomycin injury in mice, we observed that Rtel1 was most highly expressed in the lung epithelium, and its expression was reduced in PF epithelial cells compared to nonfibrotic controls. While global deletion of Rtel1 leads to embryonic lethality, constitutive deletion of Rtel1 in the lung epithelium (Rtel Δepi ) led to normal lung structure and architecture. Rtel1 Δepi mice exhibited accelerated telomere attrition and impaired AEC progenitor potential ex-vivo . Despite decreased AEC progenitor function, no differences in lung fibrosis were observed in Rtel Δepi mice compared to controls following single-dose or repetitive intratracheal bleomycin. Together, these data implicate RTEL1 as a regulator of AEC progenitor function but this level of progenitor dysfunction is not alone sufficient to cause or exacerbate experimental lung fibrosis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.000 | 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) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".