Lgr5+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors

The study investigated the role of actively proliferating Lgr5+ skin stem cells in skin carcinogenesis using Lgr5-EGFP-Ires-CreERT2/R26R-LacZ mice. These stem cells, located deep in hair follicles, were hypothesized to potentially transform into tumor-initiating cells. However, during chemical and UV carcinogenic regimens, Lgr5+ cells remained confined to hair follicles and deep-seated cysts, and their progeny were only found in the interfollicular epidermis under certain conditions. Importantly, Lgr5+ stem cells were absent in the final tumor masses, and no tumors were a result of clonal expansion of these cells, as evidenced by 52 tumors with tamoxifen at the start of carcinogenesis and 42 tumors with tamoxifen during tumor outgrowth. This indicated that, unlike CD34/K15+ quiescent bulge stem cells, Lgr5+ stem cells did not act as tumor drivers in this experimental model of skin carcinogenesis.