Epigenetic division counter times stem cell fate in the Drosophila gut
Drosophila intestinal stem cells count their self-renewal divisions to time multipotent fate switching: after producing an enteroendocrine mother cell (EMC) they complete eight divisions to generate enterocytes (ECs), and at the ninth division switch back to EMC production for enteroendocrine cells (EECs). This division-counting memory is driven by opposing histone marks—TrxG-dependent H3K4me3 and H3K36me3 decline while PcG-dependent H3K27me3 accumulates—triggering fate switching once a threshold is reached. Transient Notch signaling from EMCs initiates the count, and the system is tunable via TrxG/PcG activity while remaining resilient to injury, with implications for engineered tissue growth and differentiation-d disorder therapies.
