Activated Notch1 Redirects CD4-Fated CD4 <sup>+</sup> CD8 <sup>+</sup> Precursors to the CD8 Lineage During Thymocyte Selection Without Causing T Cell Leukemia
Bibliographic record
Abstract
ABSTRACT Positive selection of CD4/CD8 double-positive (DP) thymocytes generates helper and cytotoxic T lineages whose CD4 or CD8 co-receptor expression matches their αβ T cell receptor (TCRαβ) specificity MHCII or MHCI, respectively. Notch1 signaling is critical for early T cell development and was suggested to regulate CD4/CD8 lineage determination during DP thymocyte selection. However, early studies expressing activated Notch1 in pre-DP progenitors did not resolve this question. Here we showed that CD4-Cre-mediated activation of canonical Rbpj -dependent Notch1 signalling potently skews DP selection to the CD8 lineage. We used a tamoxifen-inducible “time-stamp” model coupled with phenotypic staging to show that that activated Notch1 decreases generation of Gata3 + CD4 + CD8 lo selection intermediates during the earliest stages of DP selection, thereby preventing ThPOK induction and emergence of CD4 lineage cells. Finally, activated Notch1 efficiently re-directed DP thymocytes expressing MHCII-specific TCRαβ into the CD8 lineage. These studies show that activated Notch1 acts early during DP selection to skew selection of CD4-fated, MHCII-specific DP precursors to the CD8 lineage.
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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) | 0.002 | 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".