This repository contains scripts and files supporting the publication:
Redhai & Hirschmüller et al., An autoinhibitory feedback mechanism preserves intestinal stem cell maintenance and fate commitment (2024).
Intestinal stem cells (ISCs) continuously renew the gut epithelium by producing regionally specialized cell types, yet the mechanisms guiding lineage commitment remain poorly defined. Here, we identify a self-limiting transcriptional program, mediated by the zinc-finger transcription factor Chronophage (Cph), that drives 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 fate specification. Genetic and single-cell transcriptomic approaches revealed that Cph is required to reprogram the transcriptome of 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 triggering autophagy and cell death, thus preserving ISC function. Our findings uncover a key regulatory mechanism that balances ISC self-renewal with lineage commitment.
Should you encounter any issues or have any questions please contact Nick Hirschmüller or Siamak Redhai.
Raw sequencing read data along with count matrices and metadata for each sample were deposited at GEO under the Study ID: GSE276185.
scRNA-seq data
Analyzed by Nick Hirschmüller and Erica Valentini.
Processed Seurat objects that can be used to reproduce figures are deposited on Zenodo: https://doi.org/10.5281/zenodo.17716158
The code to reproduce all analyses is located in the scRNAseq/analyses folder. If you run all the scripts in order, all necessary output files will be generated to create the figures from the paper (scripts located in the scRNAseq/figures folder).
NanoDam, DamID, CHIP-seq and bulk RNAseq data
Analyzed by Stefan Peidli.
The code to reproduce all analyses is located in the NanoDam_DamID_CHIPseq_RNAseq folder.
Data explorer (ShinyApp)
Created by Nick Hirschmüller.
The code to recreate the app is located in the ShinyApp folder.