Basal Cell Carcinomas Arise from Hair Follicle Stem Cells in Ptch1+/− Mice

SummaryBasal cell carcinomas (BCCs) are hedgehog-driven tumors that resemble follicular and interfollicular epidermal basal keratinocytes and hence long have been thought to arise from these cells. However, the actual cell of origin is unknown. Using cell fate tracking of X-ray induced BCCs in Ptch1+/− mice, we found their essentially exclusive origin to be keratin 15-expressing stem cells of the follicular bulge. However, conditional loss of p53 not only enhanced BCC carcinogenesis from the bulge but also produced BCCs from the interfollicular epidermis, at least in part by enhancing Smo expression. This latter finding is consistent with the lack of visible tumors on ears and tail, sites lacking Smo expression, in Ptch1+/− mice.

► Cell fate mapping pinpoints the bulge stem cell as the site of origin of Ptch1+/− BCCs ► p53 loss in the bulge enhances BCC carcinogenesis from the follicle ► p53-deficient interfollicular epidermis expresses Smo and can produce BCCs ► BCCs may differ histologically depending on their origin from follicle versus IFE