Evidence that injury can cause <i>Drosophila</i> gut differentiated, polyploid enterocytes to be recruited as stem cells via paligenosis

Differentiated cells can return to a progenitor-like state in response to injury via the evolutionarily conserved cellular program called paligenosis. Paligenosis proceeds by three stages: 1) autophagy/autodegradation of differentiated cell architecture, 2) metaplasia/progenitor gene induction, 3) TOR complex 1 (TORC1)-dependent cell cycle re-entry. Using multiple injury and reverse-lineage-tracing approaches in the <i>Drosophila</i> gut, we show that mature polyploid enterocytes dedifferentiate into diploid progenitors in response to epithelial injury. Several key findings suggest a role for paligenosis. Shortly after injury, enterocytes dramatically increased autophagic flux (stage 1); additionally, pharmacological and genetic inhibition of autophagy blocked progenitor recruitment. Rapamycin also blocked recruitment, indicating that TORC1 is required (stage 3). Finally, RNAi knockdown of <i>ifrd1</i>, an evolutionarily conserved protein required for paligenosis, blocked progenitor recruitment. Thus, replenishment of diploid progenitors from differentiated polyploid cells may occur by paligenosis. The <i>Drosophila</i> gut may offer a versatile system for dissecting the mechanisms of this evolutionarily conserved pathway.