TY - JOUR TI - Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes AU - Ruiz-Vega, Rolando AU - Chen, Chi-Fen AU - Razzak, Emaad AU - Vasudeva, Priya AU - Krasieva, Tatiana B AU - Shiu, Jessica AU - Caldwell, Michael G AU - Yan, Huaming AU - Lowengrub, John AU - Ganesan, Anand K AU - Lander, Arthur D A2 - White, Richard M A2 - Robles-Espinoza, C Daniela A2 - Adams, Peter A2 - Gómez-Schiavon, Mariana A2 - Arnheiter, Heinz VL - 9 PY - 2020 DA - 2020/10/13 SP - e61026 C1 - eLife 2020;9:e61026 DO - 10.7554/eLife.61026 UR - https://doi.org/10.7554/eLife.61026 AB - 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. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of ‘oncogene-induced senescence’. Using a mouse model of Braf-driven nevus formation, analyzing both proliferative dynamics and single-cell gene expression, we found no evidence that nevus cells are senescent, either compared with other skin cells, or other melanocytes. We also found that nevus size distributions could not be fit by any simple cell-autonomous model of growth arrest, yet were easily fit by models based on collective cell behavior, for example in which arresting cells release an arrest-promoting factor. We suggest that nevus growth arrest is more likely related to the cell interactions that mediate size control in normal tissues, than to any cell-autonomous, ‘oncogene-induced’ program of senescence. KW - nevus KW - melanocytes KW - braf mutation KW - oncogene induced senescence KW - nevus mouse model KW - skin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -