Faculty Opinions recommendation of BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells.
Bibliographic record
Abstract
During chronic infection and cancer, a self-renewing CD8+ T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8+ T cells diverge from other CD8+ subsets early after chronic viral infection. However, pathways guarding stem-like CD8+ T cells against terminal exhaustion remain unclear. Here, we show that the gene encoding transcriptional repressor BACH2 is transcriptionally and epigenetically active in stem-like CD8+ T cells but not terminally exhausted cells early after infection. BACH2 overexpression enforced stem-like cell fate, whereas BACH2 deficiency impaired stem-like CD8+ T cell differentiation. Single-cell transcriptomic and epigenomic approaches revealed that BACH2 established the transcriptional and epigenetic programs of stem-like CD8+ T cells. In addition, BACH2 suppressed the molecular program driving terminal exhaustion through transcriptional repression and epigenetic silencing. Thus, our study reveals a new pathway that enforces commitment to stem-like CD8+ lineage and prevents an alternative terminally exhausted cell fate. PMID: 33574619 Funding information This work was supported by: NIAID NIH HHS, United States Grant ID: R01 AI105343 Intramural NIH HHS, United States Grant ID: ZIA AI001240 NIAID NIH HHS, United States Grant ID: P01 AI108545 Intramural NIH HHS, United States Grant ID: ZIA BC011480 NIA NIH HHS, United States Grant ID: R00 AG056524 Intramural NIH HHS, United States Grant ID: ZIA AR041159 Intramural NIH HHS, United States Grant ID: ZIA AR041167 NIAID NIH HHS, United States Grant ID: R01 AI115712 NIA NIH HHS, United States Grant ID: K99 AG056524 NIAID NIH HHS, United States Grant ID: U19 AI082630 NCI NIH HHS, United States Grant ID: F99 CA234842 Intramural NIH HHS, United States Grant ID: ZIA NS003112 Intramural NIH HHS, United States Grant ID: ZIA DK075149 NCI NIH HHS, United States Grant ID: P01 CA210944 Intramural NIH HHS, United States Grant ID: ZIA AR041106 Intramural NIH HHS, United States Grant ID: ZIA NS003111 NCI NIH HHS, United States Grant ID: K00 CA234842 NIAID NIH HHS, United States Grant ID: P01 AI112521 NIAID NIH HHS, United States Grant ID: U19 AI117950 Intramural NIH HHS, United States Grant ID: ZIA AI001241 More Less keyboard_arrow_down
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.475 | 0.159 |
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".