A Foxo1-Klf2-S1pr1-Gnai1-Rac1 signaling axis is a critical mediator of Ostm1 regulatory network in T lymphopoiesis
Bibliographic record
Abstract
Ostm1 mutations cause the severe form of osteopetrosis with bone marrow deficiency in humans and mice, yet a role in T cell ontogeny remains to be determined. Herein, we show that thymi of the Ostm1 -null mice (gl/gl) from P8-to-P15 become markedly hypocellular with disturbed architecture. Analysis of gl/gl early T cell program determined a major decrease of 3-fold in bone marrow common lymphoid precursors (CLP), 35-fold in early thymic precursors (ETPs) and 100-fold in T cell double positive subpopulations. Ostm1 ablation in T cell double negative (DN) also appears to induce fast-paced differentiation kinetics with a transitory intermediate CD44 + CD25 int subpopulation. Transgenic targeting Ostm1 expression from the gl/gl DN1 population partially rescued T cell subpopulations from ETP onwards and normalized the accelerated DN differentiation, indicating a cell-autonomous role for Ostm1 . Transcriptome of early DN1 population identified an Ostm1 crosstalk with a Foxo1-Klf2-S1pr1-Gnai1-Rac1 signaling axis. Our findings establish that Ostm1 is an essential regulator of T cell ontogeny.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".