Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus
Bibliographic record
Abstract
Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs). Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs) in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of the present study were therefore i) to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury, and ii) to characterize their phenotypic and molecular profiles using flow cytometry, immuno-histology and transcriptome sequencing. Based on label-retention and BrdU labeling assays, we now report that while UEA1+ TECs proliferate actively in steady-state conditions, they undergo proliferative arrest and cell loss following irradiation. On the opposite, the UEA1–quiescent TECs are radioresistant and proliferate in situ following acute thymic injury, thereby contributing to thymic regeneration in 28-30 week-old mice. Most UEA1– quiescent TECs display an undifferentiated phenotype (co-expression of K8 and K5 cytokeratins) and express high levels of genes that regulate stem cell activity in different tissues (e.g., Podxl, Ptprz1). Additionally, two features suggest that UEA1– quiescent TECs occupy discrete stromal niches: i) their preferential location in clusters adjacent to the cortico-medullary junction, and ii) their high expression of genes involved in crosstalk with mesenchymal cells. Together with their undifferentiated phenotype and their high expression of stemness-associated genes, the ability of UEA1– quiescent TECs to participate to TEC regeneration qualifies them as in vivo relevant TEPCs.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".