Author Response: Dynamics of Nevus Development Implicate Cell Cooperation in the Growth Arrest of Transformed Melanocytes

September 2020

Rolando Ruiz‐Vega, Chi-Fen Chen, Emaad Razzak, Priya Vasudeva, Tatiana B. Krasieva, Jessica Shiu, Michael G Caldwell, Huaming Yan, John Lowengrub, Anand K. Ganesan, Arthur D. Lander

nevus melanocytes BRAF V600E oncogene-induced senescence single-cell RNA-seq growth arrest cell interactions mathematical models Monte Carlo mole skin cells BRAF mutation senescence RNA sequencing growth stop cell cooperation math models Monte Carlo simulation

TLDR Moles may stop growing because of cell cooperation, not just because of aging cells.

Ruiz-Vega and collaborators challenged the idea that nevi growth arrest is due to oncogene-induced senescence by analyzing single-cell RNA-seq data from BRAF V600E-expressing mouse melanocytes and found no evidence of senescence. Their mathematical models suggested that nevi size distribution is better explained by cooperative mechanisms similar to normal tissue size control, proposing that growth arrest in nevi is mediated by cell interactions. The reviewers found the manuscript clear and convincing. The authors addressed reviewer comments by clarifying arrest probabilities in figures, explaining Monte Carlo time steps in their modeling, and including additional analysis in the supplementary material.

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