Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lympho-myeloid lineage commitment outcomes (36.27)
Bibliographic record
Abstract
Abstract In the thymus, Notch signaling is known to be essential for T-lymphopoiesis, with the Notch ligand Delta like 4 (Dll4) being uniquely involved in this process. However, using stromal cell cultures, either Dll4 or Dll1 has been shown to support T-lymphopoiesis. To address which Dll is more effective at inducing hematopoietic progenitor cells to give rise to T-lineage cells in vitro, we generated OP9 cells expressing a series of incrementally discrete and equivalent levels of Dll1 or Dll4. In keeping with previous findings, OP9 cells expressing high levels of either Dll1 or Dll4 gave rise to T-lineage cells with similar efficacy, and prevented the differentiation of B- and myeloid-lineage cells. However, at limiting levels of Dll expression, Dll4 maintained its ability to inhibit B-lineage choice and induce T-lineage commitment and differentiation at lower levels of expression than Dll1. This manifest property of Dll4 is evident despite its lower levels of steady-state surface expression than Dll1 on OP9 cells. The heightened effectiveness of Dll4 over Dll1 also corresponded to the induction of expression of Notch target genes, and inhibition of B- and myeloid-specific transcription factors. Furthermore, OP9 cells expressing levels of Dll4 equivalent to those present in thymic epithelial cells gave rise to T-lineage cells, as expected, but were also permissive for the differentiation of myeloid cells, while still inhibiting the generation of B-lineage cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".