SATB1 is essential in regulating the stemness of antigen-specific CD8+ T cells
Bibliographic record
Abstract
Abstract In chronic infection and cancer, a subset of self-renewing, antigen-specific CD8+ T cells, termed progenitors, is crucial for long-term immunity and immunotherapy effectiveness. The mechanisms governing their stemness, however, are not fully understood. Our single-cell RNA + ATAC sequencing analysis revealed that SATB1 (special AT-rich sequence-binding protein) is exclusively expressed in the progenitor CD8+ T cells during chronic infection. Known for its key role in chromatin organization during T-cell development, SATB1’s unique expression in the progenitor CD8+ T cell led us to hypothesize that it plays a pivotal role in regulating the stemness of the antigen-specific CD8+ T cells. Using the lymphocytic choriomeningitis virus (LCMV) Clone 13 mouse model of chronic infection, the SATB1 gene was deleted in CD8+ T cells via CRISPR/ RNP technology. At day 21 post-infection, the SATB1 deletion resulted in a reduction of virus-specific progenitor CD8+ T cells and a decrease of TCF1 expression. The transcriptomic and epigenomic studies further revealed that SATB1 plays a key role in regulating the chromatin accessibility and transcriptional activities of stemness-associated genes, such as Tcf7, Bach2, and Myb. Overall, our results underscore the critical role of SATB1 in maintaining the transcriptional integrity of progenitor CD8+ T cells in response to antigen activation, which sheds light on the genetic pathways that regulate the stemness of antigen-specific CD8+ T cells.
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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) | 0.002 | 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".