Autophagy inhibition in intestinal stem cells favors enteroendocrine cell differentiation through Stat92E activity
Bibliographic record
Abstract
Because the intestinal epithelium is exposed to various stressors, dysregulation of essential mechanisms that maintain gut homeostasis, such as autophagy, has been linked to inflammatory bowel pathologies. In Drosophila melanogaster, inhibition of autophagy specifically in adult intestinal stem cells (ISCs) affects their proportions differently during aging. Proper intestinal renewal requires a balance between ISC proliferation and differentiation. Here, we showed that, in adult ISCs, loss of core autophagy genes and regulators of autophagosome-lysosome fusion increases the enteroendocrine cell population and enhances the transcriptional activity of Stat92E. Functional experiments involving cell fate regulators of enteroendocrine or enterocyte differentiation and proliferation suggested that dysfunctional autophagy in adult ISCs enhances Stat92E activity downstream of Hop/JAK kinase. Finally, lineage-tracing analyses confirmed that autophagy inhibition promotes enteroendocrine cell differentiation. Thus, our data demonstrate that, under homeostatic conditions, basal autophagy limits enteroendocrine cell differentiation by regulating Stat92E activity, which can be counteracted by the transcription factor Scute.
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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 | 0.000 |
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".