Basal Cell Carcinomas in Mice Arise from Hair Follicle Stem Cells and Multiple Epithelial Progenitor Populations

The study demonstrated that basal cell carcinomas (BCCs) in mice could originate from hair follicle stem cells, particularly from the secondary hair germ and lowermost bulge regions, as well as from multiple epithelial progenitor populations. Using a triple-transgenic mouse model, researchers induced GLI2ΔN expression to activate the Hedgehog signaling pathway, leading to BCC-like tumor development. Nodular BCC-like tumors arose from K15+ and Lgr5+ stem cells, with rapid development on the snout and dorsal paws. While bulge stem cells showed resistance to GLI2ΔN-induced hyperplasia due to lower proliferation and increased apoptosis, other regions like the secondary hair germ were more susceptible. The study also found that GLI2ΔN was a more potent oncogenic driver than SMO, leading to aggressive tumor forms, and that tumor development was more rapid during the anagen phase of the hair cycle.