Autophagy inhibition in intestinal stem cells favors enteroendocrine cell differentiation through Stat92E activity
Bibliographic record
Abstract
ABSTRACT Because the intestinal epithelium faces many stresses, dysregulation of essential mechanisms governing gut homeostasis, such as autophagy, has been associated with inflammatory bowel pathologies. In Drosophila melanogaster , the inhibition of autophagy, specifically in adult intestinal stem cells (ISCs), affects their number differently through aging. Appropriate intestinal renewal requires a balance between ISC proliferation and differentiation. Herein, we show that in adult ISCs, the loss of core autophagy genes and regulators of autophagosome-lysosome fusion increased the enteroendocrine cell population and transcriptional activity of Stat92E. Functional experiments with cell fate regulators involved in enteroendocrine or enterocyte differentiation or proliferation suggested that dysfunctional autophagy in adult ISCs enhanced Stat92E activity downstream of Hop/JAK kinase. Finally, lineage-tracing analyses confirmed that autophagy inhibition autonomously promotes enteroendocrine cell differentiation without affecting enterocyte differentiation. Thus, our data demonstrates that, under homeostatic conditions, basal autophagy limits enteroendocrine cell differentiation by controlling Stat92E activity.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".