Notch signaling requires GATA-3 for the survival of cells entering the T-lineage development program (64.4)
Bibliographic record
Abstract
Abstract GATA-3 plays a crucial role in T cell development, however its role and collaboration with the Notch signaling pathway in the induction of T cell specification and commitment have not been fully elucidated. Work in our laboratory using both, in vitro and in vivo models of T cell development, has shown that GATA-3 deficiency arrests this development at the DN2 stage but does not result in B-lymphopoiesis in the presence of Notch ligand Delta-like 1 (Dll1). These GATA-3-/- progenitors express T-lineage associated genes but are unable to survive the T-specification event as indicated by their increased rate of apoptosis. Cell cycle regulation genes, mainly p19Arf and p16Ink4a (Arf/Ink), are upregulated in these cells as indicated by gene expression microarray and qRT-PCR analyses. We have thus sought to address the possibility that GATA-3 represses Arf/Ink following T cell specification/commitment in the presence of Notch signals. We are employing ChIP assay to show whether potential GATA-3 recognition sequences present in the Arf/Ink promoter region are occupied and regulated by GATA-3. Finally, using GATA-3-/-Arf-Ink-/- bone marrow progenitors, we will address a possible rescue of the early T cell developmental block observed in the absence of GATA-3. These experiments will help to identify a potential mechanism of how GATA-3 and the Notch signaling pathway collaborate in regulating T-lineage specification, commitment and survival during T cell development.
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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".