# Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation

## TL;DR

This study compares how melanocytes from dark and light-skinned individuals respond to UVB radiation and their environment, revealing differences in gene activity and signaling pathways.

## Contribution

The study identifies novel interactions between ribosomal proteins and P53 signaling in melanocytes under UVB stress and highlights evolutionary roles of MIF and ATP6V0B.

## Key findings

- Differential gene expression in dark and light melanocytes occurs within 6 hours of UVB exposure, linked to inflammation and melanoma.
- KCM+ culture activates mTOR pathways in light melanocytes, affecting metabolism and survival.
- Natural selection analysis supports MIF and ATP6V0B as evolutionarily significant for pigmentation.

## Abstract

We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.