The study investigates the relationship between Lgr5 stem cells and Paneth cells in the intestinal crypts. Lgr5 stem cells, located at the bottom of intestinal crypts, are interspersed with Paneth cells, which produce bactericidal substances. Single Lgr5 stem cells can form long-lived, self-organizing crypt-villus organoids in vitro. The research shows that Lgr5 stem cells are physically associated with Paneth cells and that Paneth cells express essential signals for stem cell maintenance, such as EGF, TGFα, Wnt3, and the Notch ligand Dll4. Co-culturing Lgr5 stem cells with Paneth cells significantly improves organoid formation, and this requirement can be mimicked by exogenous Wnt signaling. Genetic removal of Paneth cells results in the loss of Lgr5 stem cells, indicating that Paneth cells provide essential niche support. In colon crypts, CD24⁺ cells, which may represent Paneth cell equivalents, reside between Lgr5 stem cells. The study concludes that Lgr5 stem cells compete for niche signals provided by Paneth cells, highlighting the multifunctional role of Paneth cells in maintaining intestinal homeostasis.The study investigates the relationship between Lgr5 stem cells and Paneth cells in the intestinal crypts. Lgr5 stem cells, located at the bottom of intestinal crypts, are interspersed with Paneth cells, which produce bactericidal substances. Single Lgr5 stem cells can form long-lived, self-organizing crypt-villus organoids in vitro. The research shows that Lgr5 stem cells are physically associated with Paneth cells and that Paneth cells express essential signals for stem cell maintenance, such as EGF, TGFα, Wnt3, and the Notch ligand Dll4. Co-culturing Lgr5 stem cells with Paneth cells significantly improves organoid formation, and this requirement can be mimicked by exogenous Wnt signaling. Genetic removal of Paneth cells results in the loss of Lgr5 stem cells, indicating that Paneth cells provide essential niche support. In colon crypts, CD24⁺ cells, which may represent Paneth cell equivalents, reside between Lgr5 stem cells. The study concludes that Lgr5 stem cells compete for niche signals provided by Paneth cells, highlighting the multifunctional role of Paneth cells in maintaining intestinal homeostasis.