Human sensory neurons modulate melanocytes through secretion of RGMB.

Melanocytes are surrounded by diverse cells, including sensory neurons in our skin, but their interaction and functional importance have been poorly investigated. In this study, we find that melanocytes and nociceptive neurons contact more in human skin color patch tissue than control. Co-culture with human iPSC-derived sensory neurons significantly induces morphogenesis and pigmentation of human melanocytes. To reveal melanocyte-stimulating factors secreted from neurons, we perform proteomic analyses and identify RGMB in the sensory neuron-conditioned medium. RGMB protein induces morphogenesis and melanin production of melanocytes, demonstrating that RGMB is a melanocyte-stimulating factor released from sensory neurons. Transcriptome analysis suggests that the melanosome transport machinery can be controlled by RGMB, leading us to identify the vesicle production response of melanocytes upon RGMB treatment. This study discovers a role of sensory neurons in modulating multiple aspects of human melanocytes through secretion of a key factor: RGMB.