Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion

Significance The stem cell niche is the in vivo microenvironment in which stem cells both reside and receive stimuli that determine their fate. Intestinal Paneth cells produce an arsenal of molecules involved in numerous biological processes, including critical support of the intestinal stem cell niche via the expression of niche ligands, growth factors, and cytokines. The relevance of the niche function of Paneth cells has been challenged, however. Here we show that specific, acute ablation of Paneth cells in mice does not affect the stem cell population, because alternative niche cells derive enteroendocrine and tuft cells. These cells serve as an alternative source of Notch signals, which are essential for intestinal stem cell maintenance.