Shown are three-dimensional (3D) mouse enteroid-derived C57Bl/6 mouse crypts after Hoechst staining under observation by confocal microscopy. Enteroids are small intestine organoids containing fully differentiated and polarized epithelium with a central lumen. This novel 3D culture model allows deeper investigation of small intestine radiotoxicity, which is a common side effect of abdominal radiation therapy. The use of enteroids culture reveals how the sphingolipid ceramide and its hydrolysis enzyme, the acid sphingomyelinase secreted by irradiated endothelial cells, are modulating size, shape, and number of enteroids after radiation. For details, see article by Leonetti and colleagues on page 2651.