Together these data imply that epithelial ligand-independent Wnt signaling mutation (such as APC) enhances fitness of the CBC stem cell phenotype, whereas RSC fitness may be influenced by signaling disruption from both epithelial cell-intrinsic (e.g. KRAS and BRAF) and tumor microenvironmental sources, with some key pro-regenerative stem cell pathways mapping predominantly to immune (IFN-γ), stromal (TGFβ), and matrix (YAP) cell compartments. The gene discussed is KRAS; the disease is neoplasm.