The intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports a model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes to epithelial regeneration upon ablation of injury-sensitive stem cells. However, such facultative stem cell activity is rare within secretory populations. Here we ask whether specific functional properties predict facultative stem cell activity. We utilize in vivo labeling combined with ex vivo organoid formation assays to evaluate how cell age and autophagic state contribute to facultative stem cell activity within secretory lineages. Strikingly, we find that cell age (time elapsed since cell cycle exit) does not correlate with secretory cell plasticity. Instead, high autophagic activity predicts plasticity and resistance to DNA damaging injury independently of cell lineage. Our findings indicate that autophagic status prior to injury serves as a lineage-agnostic marker for the prospective identification of facultative stem cells. In contrast to the dedifferentiation of committed secretory cells, other studies suggest that a population of dedicated, quiescent, facultative stem cells drives intestinal regeneration. Our group has previously determined that the Msi family of RNA-binding proteins are both necessary and sufficient for activation of this pool of facultative intestinal stem cells. Here we present a novel mouse model utilizing HyperTRIBE technology to identify Msi2 RNA binding partners in rare intestinal epithelial cell populations, and possibly even single cells.