Developmental progression of fetal HEB<sup>−/−</sup> precursors to the pre‐T‐cell stage is restored by HEBAlt
Bibliographic record
Abstract
Gene knockout studies have shown that the E-protein transcription factor HEB is required for normal thymocyte development. We have identified a unique form of HEB, called HEBAlt, which is expressed only during the early stages of T-cell development, whereas HEBCan is expressed throughout T-cell development. Here, we show that HEB(-/-) precursors are inhibited at the β-selection checkpoint of T-cell development due to impaired expression of pTα and function of CD3ε, both of which are necessary for pre-TCR signaling. Transgenic expression of HEBAlt in HEB(-/-) precursors, however, upregulated pTα and allowed development to CD4(+) CD8(+) stage in fetal thymocytes. Moreover, HEBAlt did overcome the CD3ε signaling defect in HEB(-/-) Rag-1(-/-) thymocytes. The HEBAlt transgene did not permit Rag-1(-/-) precursors to bypass β-selection, indicating that it was not acting as a dominant negative inhibitor of other E-proteins. Therefore, our results provide the first mechanistic evidence that HEBAlt plays a critical role in early T-cell development and show that it can collaborate with fetal thymic stromal elements to create a regulatory environment that supports T-cell development past the β-selection checkpoint.
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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) | 0.001 | 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) | 0.004 | 0.002 |
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".