Single cell gene expression of melanocyte specific Braf mutant mouse skin

Mutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented “moles”), yet the same change is the most common driver mutation in melanoma. One of the abiding mysteries of carcinogenesis is why oncogene activation doesn’t always lead to cancer. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of “oncogene-induced senescence”. Senescence is usually accompanied by distinctive gene expression and various gene expression “signatures” have been developed to help investigators identify senescent cells and distinguish them from cells that have become growth arrested by other processes. Using a mouse model of Braf-driven nevus formation, we analyzed single-cell gene expression and found no evidence that nevus cells are senescent, either compared with other skin cells, or other melanocytes. Single Cell suspensions were obtained from BrafWT, Tyr::CreER or BrafV600E, Tyr::CreER mice at either P30 (n = 2 of each genotype) or P50 (n = 3 of each genotype). RNA was isolated using 10X Genomics technologies. Under the sample titles, "WT" represents cells obtained from wild type skin, and "MT" represents cells from mice in which the Braf oncogene was activated in the melanocytic lineage.