Paneth cells serve as a niche for Lgr5 stem cells in intestinal crypts. Lgr5 stem cells are located between Paneth cells, which produce bactericidal substances. In vitro, Lgr5 stem cells can form organoids without non-epithelial cells, but co-culturing with Paneth cells enhances organoid formation. Paneth cells express signals essential for stem cell maintenance, including EGF, TGFα, Wnt3, and Notch ligand Dll4. Genetic removal of Paneth cells leads to loss of Lgr5 stem cells. In colon crypts, CD24+ cells between Lgr5 stem cells may represent Paneth cells. Lgr5 stem cells compete for niche signals from Paneth cells. In a Matrigel-based culture system, single Lgr5 stem cells grow into crypt-like structures with Paneth cells at the bottom. Confocal imaging shows a geometrical distribution of Paneth and Lgr5 cells, maximizing heterotypic contact. Paneth cells provide essential signals like EGF, Wnt3, and Notch. Exogenous Wnt3A can substitute for Paneth cells. In vivo, Paneth cell loss reduces stem cell numbers. Sox9 deletion leads to Paneth cell loss and stem cell disappearance. Paneth cells are essential for crypt and stem cell maintenance. Stem cells receive niche support from their own progeny, similar to fly testis stem cells. Lgr5 stem cells compete for Paneth cell surface. Paneth cells are born at the crypt base, the original "stem cell zone." Understanding Paneth cell regulation is important for intestinal homeostasis.Paneth cells serve as a niche for Lgr5 stem cells in intestinal crypts. Lgr5 stem cells are located between Paneth cells, which produce bactericidal substances. In vitro, Lgr5 stem cells can form organoids without non-epithelial cells, but co-culturing with Paneth cells enhances organoid formation. Paneth cells express signals essential for stem cell maintenance, including EGF, TGFα, Wnt3, and Notch ligand Dll4. Genetic removal of Paneth cells leads to loss of Lgr5 stem cells. In colon crypts, CD24+ cells between Lgr5 stem cells may represent Paneth cells. Lgr5 stem cells compete for niche signals from Paneth cells. In a Matrigel-based culture system, single Lgr5 stem cells grow into crypt-like structures with Paneth cells at the bottom. Confocal imaging shows a geometrical distribution of Paneth and Lgr5 cells, maximizing heterotypic contact. Paneth cells provide essential signals like EGF, Wnt3, and Notch. Exogenous Wnt3A can substitute for Paneth cells. In vivo, Paneth cell loss reduces stem cell numbers. Sox9 deletion leads to Paneth cell loss and stem cell disappearance. Paneth cells are essential for crypt and stem cell maintenance. Stem cells receive niche support from their own progeny, similar to fly testis stem cells. Lgr5 stem cells compete for Paneth cell surface. Paneth cells are born at the crypt base, the original "stem cell zone." Understanding Paneth cell regulation is important for intestinal homeostasis.