(A) Experimental scheme and hypothesis showing a lack of efficient melanomagenesis during MCSC quiescence (Q) periods. Tmx, tamoxifen; Tel, telogen; Ana, anagen; Cat, catagen; A, active status of MCSCs. (B) Histological phenotypes with tdTomato lineage tracing. (C) Experimental scheme and hypothesis for the role of UVB exposure in melanomagenesis through MCSC activation during the quiescent period of telogen (circled A, UVB-mediated activation). (D) Melanomagenesis via UVB irradiation during late anagen, and demonstration of melanoma initiation by tdTomato lineage tracing. (E) Early UVB-induced melanocytic hyperplasia throughout the interfollicular epidermis (IFE) demonstrated by lineage tracing. (F) Histology and tdTomato lineage tracing demonstrating UVB-induced melanomagenesis from quiescent tumor-prone MCSCs during late anagen. (G) Summary of UVB effects in melanomagenesis originating from quiescent melanoma-competent MCSCs. Activation of MCSCs is required for melanomagenesis (1, 2 and 4), UVB can significantly activate quiescent melanoma-competent MCSCs in telogen (3) and anagen (5) to induce melanomagenesis in a manner similar to human tumor initiation and progression. IF counterstaining, DAPI. Scale bars, 100 μm.