APC and colorectal carcinoma: We established colonoids from untransformed colon epithelial cells of LSL-KrasG12D+/− × Trp53fl/fl mice (NT-I) and transformed these into CRC in vitro by cre-mediated recombination of LSL-KrasG12D and Trp53fl/fl alleles and CRISPR–Cas9-mediated gene editing of Apc (Fig. 1a and Extended Data Fig. 1a–f).