PGE2—secreted into the niche by a rare population of PTGS2-expressing pericryptal fibroblasts—drives the expansion of Sca1+ reserve-like stem cells, with a regenerative/tumorigenic YAP transcriptional signature and concomitant suppression of β-catenin signalling, fuelling adenoma initiation in ApcMin/+ mice as well as an azoxymethane-induced tumour model. Here, YAP1 is linked to neoplasm.