Atoh1 secretory progenitors possess renewal capacity independent of Lgr5 cells during colonic regeneration.

During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling stem cells. However, various insults can lead to depletion of stem cells, and colonic epithelium can be regenerated from negative cells. While studies in the small intestine have addressed the lineage identity of the negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using -19 () to mark a heterogeneous population of cells, we found that negative cells can regenerate colonic crypts and give rise to stem cells. absorptive progenitor cells did not contribute to epithelial repair after injury, whereas secretory progenitors did contribute to this process. Additionally, while colonic cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis.