RANK-DEPENDENT CONTROL OF TUFT AND BEST4 CELL DEVELOPMENT IN THE INTESTINE
Bibliographic record
Abstract
Specialist intestinal epithelial cells are critical for barrier integrity and immune responses at the mucosal boundary, yet the pathways that govern their development are incompletely defined. Here, we identify an essential role for TNFRSF11A/RANK in shaping intestinal epithelial specialization in zebrafish. Using lineage trajectory analysis, we identify two tuft cell subtypes, including a subtype enriched for expression of genes required to produce pro-inflammatory leukotrienes. We show that RANK deficiency reduces the abundance of immune-regulatory tuft and BEST4 cells, increases goblet cell frequency, and promotes the accumulation of pro-inflammatory leukocytes in the gut. Functionally, we demonstrate that the number of cells expressing the BEST4 cell marker cftr expand following infection with a pandemic strain of Vibrio cholerae, and we show that RANK deficiency enhances fish susceptibility to host colonization by Vibrio, implicating this lineage in host defenses against an enteric pathogen. Together, our findings implicate RANK signaling in intestinal epithelial diversification and immune regulation.
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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 | 0.001 | 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".