Human sensory neurons modulate melanocytes through secretion of RGMB
Human sensory neurons modulate melanocytes through secretion of RGMB
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DOI：
10.1016/j.celrep.2022.111366
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发表时间：
2022-09-20
期刊：
影响因子：
8.8
通讯作者：
Ikeuchi, Yoshiho
中科院分区：
文献类型：
--
作者：
Chow, Siu Yu A.;Nakayama, Kazuki;Ikeuchi, Yoshiho
黑素细胞被不同的细胞包围，包括我们皮肤中的感觉神经元，但它们的相互作用和功能重要性一直没有得到很好的研究。在这项研究中，我们发现黑素细胞和伤害性神经元在人类皮肤颜色斑块组织中比对照更多地接触。与人IPSC来源的感觉神经元共培养可显著诱导人黑素细胞的形态发生和色素沉着。为了揭示神经元分泌的黑素细胞刺激因子，我们进行了蛋白质组学分析，并在感觉神经元条件培养液中鉴定了RGMB。RGMB蛋白诱导黑素细胞形态发生和黑素生成，表明RGMB是感觉神经元释放的一种黑素细胞刺激因子。转录组分析表明，黑素小体运输机制可以由RGMB控制，这使我们能够确定RGMB治疗后黑素细胞的囊泡产生反应。这项研究发现感觉神经元通过分泌一种关键因子：RGMB来调节人类黑素细胞的多个方面。
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 pro-duction 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.