ArticleThe EMBO journal2026
Autoinhibitory feedback preserves intestinal stem cell maintenance and fate commitment.
Article in The EMBO journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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18 authors.
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Abstract
Intestinal stem cells (ISCs) continuously renew the gut epithelium by producing specialised cell types, yet the mechanisms that couple ISC renewal with lineage commitment remain poorly characterised. Here, we identify a self-limiting transcriptional program, mediated by the zinc-finger transcription factor Chronophage (Cph), that promotes both ISC maintenance and differentiation into enteroendocrine (EE) cells in the Drosophila midgut. Cph expression is transiently induced by the proneural factor scute at the onset of ISC-to-EE specification. Genetic and single-cell transcriptomic approaches revealed that Cph is required to reprogramme ISCs and sustain normal lifespan. Cph binds to genes involved in proliferation and differentiation, and directly represses its own expression. This autoinhibitory feedback safeguards ISCs from accumulating autophagosomes and undergoing cell death, thus preserving ISC function. Our findings uncover a key regulatory mechanism that balances stem cell maintenance and differentiation, highlighting principles relevant to regenerating tissues.
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