Atoh1+ secretory progenitors possess renewal capacity independent of Lgr5+ cells during colonic regenerationThe EMBO Journal (2019)
During homeostasis, the colonic epithelium is replenished every 3–5 days by rapidly cycling Lgr5+ stem cells. However, various insults can lead to depletion of Lgr5+ stem cells, and colonic epithelium can be regenerated from Lgr5‐negative cells. While studies in the small intestine have addressed the lineage identity of the Lgr5‐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 keratin‐19 (Krt19) to mark a heterogeneous population of cells, we found that Lgr5‐negative cells can regenerate colonic crypts and give rise to Lgr5+ stem cells. Notch1+ absorptive progenitor cells did not contribute to epithelial repair after injury, whereas Atoh1+ secretory progenitors did contribute to this process. Additionally, while colonic Atoh1+ cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of Lgr5+ cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis.
Citation InformationD Castillo-Azofeifa, EN Fazio, R Nattiv, HJ Good, et al.. "Atoh1+ secretory progenitors possess renewal capacity independent of Lgr5+ cells during colonic regeneration" The EMBO Journal (2019)
Available at: http://works.bepress.com/samuel-asfaha/1/