To engineer a human model to trace the role of Lgr5+ cells, Shimokawa and colleagues used CRISPR/Cas9-mediated homologous recombination to establish Lgr5-GFP clones or KRT20-GFP clones—marking differentiated cells—of colorectal cancer organoids derived from human colorectal tumors. Here, LGR5 is linked to colorectal neoplasm.