Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity

The 2016 study by Kretzschmar et al. explored the effects of β-catenin activation in various epidermal stem cell populations on hair follicle formation and skin tumor development. They discovered that activation in LGR6+ and LRIG1+ stem cells led to ectopic hair follicles in the sebaceous gland, while LGR5+ cells did not contribute to this process. Instead, activation in LGR5+ cells resulted in pilomatricomas, LRIG1+ cells in trichoadenomas, and LGR6+ cells in dermatofibromas, each with distinct stromal characteristics. The study, which involved 3 to 5 mice per condition and time point, concluded that the specific compartment of epidermal stem cells where β-catenin is activated determines the type of skin tumor that forms, highlighting the importance of cellular origin in tumor heterogeneity.