The reason for the dark skin has been found! It may be the “pot” of sensory nerve cells

Summary:Hyperpigmentation disorders occur when melanocytes are damaged or reduced to produce too much or not enough melanin. In most pigmentation disorders, the changes in melanin are uneven, localized, and persistent, such as skin pigmentation. Skin color patches can be congenital, or they can appear with age. More recently, research has identified sensory neurons that 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 the moment when “white skin” is the beauty, many people, especially girls, are very Care about whether your skin is fair or not. We know that human skin color is composed of four biological pigments, including dark-brown melanin, red oxyhemoglobin, violet-blue deoxyhemoglobin, and yellow carotene. Among them, melanin is the main cause of darkening of the skin, various pigmentation spots, and uneven skin tone. When melanocytes are damaged or reduced to produce excessive or insufficient melanin, pigmentation disorders occur.

Researchers from the University of Tokyo’s Institute of Industrial Science attempted to explore the role of skin sensory neurons in melanosis. They found that sensory neurons stimulated by secreting repulsion guide molecule B (RGMB) Melanocytes produce melanin, which in turn causes melanosis. The research results were published in Cell Reports under the title of “Human sensory neurons modulate melanocytes through secretion of RGMB”.

Figure 1 Research results (Source: [1])

Based on observations of neuron-melanocyte contacts in human skin, researchers hypothesized that interactions between neurons and melanocytes can cause changes in pigmentation or melanocyte morphology . To test the hypothesis, the researchers established a co-culture model of melanocytes with human induced pluripotent stem cell (IPSC)-derived nociceptive sensory neurons. Comparing melanocytes with and without co-culture with neurons, it was found that when co-cultured with neurons, the pigmentation of melanocytes was significantly increased, suggesting that sensory neurons can directly regulate melanocyte activity strong>.

To study the mechanism by which sensory neurons stimulate melanocytes, the researchers collected iPSC-derived sensory neuron-conditioned medium (hSN-CM) and used it to culture melanocytes,Melanocytes cultured in hSN-CM were found to show increased cell survival and dendritic length, suggesting that neurons produce and secrete certain factors into mediators capable of regulating melanocyte activity. Identification of proteins secreted by neurons revealed that repulsive targeting molecule B (RGMB) is a secreted factor that activates melanocytes.

Fig.2 Identification of RGMB secreted by neurons as melanocyte activator (Source: [1])

Next, the researchers analyzed the abundance of RGMB in human skin to determine the possible contribution of RGMB from neurons to melanocytes. Immunohistochemical analysis of RGMB-stained human skin sections co-localized with peripherin-positive skin neurons confirmed that RGMB in the skin was mainly derived from skin neurons.

Following single-gene sequencing analysis, researchers found that RGMB not only regulates melanin production, but also melanin transport through the production of melanosomes. showed that RGMB is a key regulator of melanocytes, with the ability to modulate melanocyte activity and regulate vesicle release in addition to regulating morphogenesis and melanogenesis.

In this study, researchers used human skin and in vitro cultures to explore the relationship between neurons and melanocytes. They first visualized the interaction between neurons and melanocytes in human skin and reproduced this interaction by co-culturing human sensory neurons with melanocytes. Ultimately, it was found that melanocytes co-cultured with neurons improved survival and pigmentation.

Using a proteomic approach,researchers identified proteins secreted by sensory neurons, including repulsion-directing molecule B (RGMB), and found that RGMB promotes melanocyte survival and Pigmentation. This finding underscores the importance of sensory neurons in skin pigmentation and physiology. RGMB regulates not only melanocytes, but other skin cells as well, paving the way for the development of new drugs to treat neurocutaneous diseases and skin pigmentation disorders.

Writing | Mu Zijiu

Typesetting|Mu Zijiu


[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.

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