The BTG/TOB family protein TIS21 regulates stage‐specific proliferation of developing thymocytes
Bibliographic record
Abstract
As thymocytes undergo differentiation in the thymus, they progress through distinct phases of quiescence and proliferation. Identifying cellular mechanisms that maintain thymocytes in a non-dividing state is critical to fully understand T cell development. A member of the B cell translocation gene/transducer of ErbB-2 (BTG/TOB) family of anti-proliferative proteins was identified as a key mediator of the quiescent state in peripheral anergic and unstimulated T cells. Here, we demonstrate that the BTG/TOB family member TPA-inducible sequence 21 (TIS21) is expressed in quiescent CD44+ CD25- early progenitor thymocytes and CD44- CD25+ cells prior to TCR beta-selection. However, TIS21 expression is decreased in proliferating CD25+ CD44+ progenitor thymocytes and CD25(low) CD44- beta-selected cells, suggesting that its regulated expression may enable thymocytes to remain quiescent in the absence of mitogenic signals. We addressed the role of TIS21 in regulating thymocyte stage-specific expansion by ectopically expressing TIS21 in developing thymocytes and hematopoietic progenitors. Dysregulated expression of TIS21 inhibited the expansion of thymocytes even in the presence of endogenous mitogenic signals, while thymocyte differentiation was unimpeded. These findings imply that the intracellular mechanisms regulating thymocyte differentiation and proliferation, which are induced downstream of developmental cues, function independently during early T cell development.
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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) | 0.000 | 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 | 0.000 |
| 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".