Abstract: When melanocytes are damaged or reduced and excessive or insufficient melanin is produced, pigmentation disorders occur. In most pigmentation disorders, the changes in melanin are uneven, local and long-lasting, such as skin pigmentation. Skin color patches may be congenital or may appear with age. Recently, studies have discovered that sensory neurons play a role in human skin pigmentation.
Skin is not only an intuitive reflection of a person's appearance, but also an important physical barrier that separates the human body from the outside world. At a time when "white skin" is beautiful, many people, especially girls, care about whether their skin is white and whether it is good or not. We know that human skin color consists of four biological pigments, including black-brown melanin, red oxyhemoglobin , purple-blue deoxyhemoglobin and yellow carotene . Among them, melanin is the main reason for darkening of the skin, various pigmentation spots, and uneven skin tone. When melanocytes are damaged or reduced and excessive or insufficient melanin is produced, pigmentation disorders will occur.
Researchers from the Institute of Industrial Science at the University of Tokyo tried to explore the role of skin sensory nerve cells in melanin deposition. They found that sensory neurons stimulate melanin to produce melanin by secreting repulsive guide molecule B (RGMB), which in turn leads to melanin deposition. The research results were titled "Human sensing neurons modulate melanocytes through secretion of RGMB" and were published on Cell Reports.
Figure 1 Research results (Photo source: [1])
Based on observations on the contact between neurons and melanocytes in human skin, the researchers hypothesized that the interaction between neurons and melanocytes can cause pigmentation or changes in melanocyte morphology. To test the hypothesis, the researchers established a co-culture model of melanocytes and human-induced pluripotent stem cells (IPSCs)-derived nociceptive sensory neurons. Comparing melanocytes with and without co-cultured with neurons, found that the pigmentation of melanocytes increased significantly when co-cultured with neurons, suggesting that sensory neurons can directly regulate melanocyte activity .
To study the mechanism by which sensory neurons stimulate melanocytes, the researchers collected iPSC-derived sensory neuron culture medium (hSN-CM) and used to culture melanocytes. found that melanocytes cultured in hSN-CM showed increased cell survival and dendritic length, indicating that neurons produce certain factors and secrete them into media that can regulate melanocyte activity . The protein secreted by neurons was identified and it was found that the rejection directed molecule B (RGMB) is a secretory factor that can activate melanocytes.
Figure 2 The identification of the RGMB secreted by neurons is a melanocyte activator (Figure source: [1])
Next, the researchers analyzed the abundance of RGMB in human skin to determine the possible contribution of RGMB from neurons to melanocytes. Chemical analysis of immuno-tissue in human skin sections colocalized with peripheral protein-positive skin neurons confirmed that RGMB in the skin mainly comes from skin neurons.
After single-gene sequencing analysis, the researchers found that RGMB not only regulates the production of melanin, but also regulates the transportation of melanin through the production of melanosomes. It is shown that RGMB is a key regulator of melanocytes and has the ability to regulate melanocyte activity and vesicle release in addition to regulating morphogenesis and melanin production.
In this study, the researchers used human skin and in vitro culture to explore the relationship between neurons and melanocytes. They first visualized the role between neurons and melanocytes in human skin and reproduced this interaction through co-culture of human sensory neurons and melanocytes. It was eventually found that melanocytes co-cultured with neurons improved survival and pigmentation.
Through the proteomics method, researchers identified sensory neuron secreted proteins including the rejection-directing molecule B (RGMB), and found that RGMB promoted melanocyte survival and pigmentation . This finding emphasizes the importance of sensory neurons in skin pigmentation and physiology .RGMB can regulate not only melanocytes, but also other skin cells, paving the way for the development of new drugs for treating neurodermal diseases and skin pigmentation disorders.
Written by | Muzijiu
Typesetting | Muzijiu
End
Reference materials:
[1]Chow SYA, Nakayama K, Osaki T, et al. Human sensory neurons modulate melanocytes through secretion of RGMB. Cell Rep. 2022 Sep 20;40(12):111366. doi: 10.1016/j.celrep.2022.111366. PMID: 36130522.
This article is original by Biological Exploration, and personal forwarding and sharing are welcome. If any other media or website needs to be reproduced, the source of Bio-Exploration must be indicated in front of the main text.