This is consistent with the finding that about 50% of MMRd/MSI-H CRC had Lgr5 expression (82) and indicates that tumor cells were initiated either solely from Lgr5+ cells (with some of them differentiating to Lgr5− cells during tumor progression) or from both Lgr5+ stem cells and Lgr5− progenitor cells in the transit amplifying (TA) zone (since Villin-Cre is expressed in intestine epithelial cells all along the crypt-villus axis) (83). Here, LGR5 is linked to colorectal carcinoma.