The article titled “Signalling by senescent melanocytes hyperactivates hair growth” in the journal Nature is a research study that investigates the role of senescent melanocytes in hair growth. Senescent melanocytes are a type of cell that can be found in the skin. These cells, under specific conditions, can affect the behavior of hair stem cells. Stem cells, in general, can remain inactive for extended periods or can be activated briefly to enable regeneration. The signals that control whether stem cells remain inactive or become active are known as niche signals. When these signals are balanced, stem cells function properly, but if there is an imbalance in these signals, it can cause regenerative (and indeed degenerative) disorders.
One of the phenomena observed in humans is that melanocytic skin nevi often display excessive hair growth. Melanocytic skin nevi, commonly known as moles, are usually small dark spots on the skin due to the high concentration of melanocytes. The excessive hair growth in these nevi implies that there may be hyperactivity in hair stem cells. In this study, the researchers explored the connection between senescent melanocytes and the activity of hair stem cells.
To study this, the researchers used genetic mouse models of nevi and human skin tissue samples. They observed that clusters of senescent melanocytes in the dermal layer of the skin could drive epithelial hair stem cells to become active. More specifically, these melanocytes can cause the hair stem cells to exit a state of inactivity known as quiescence. In addition, the senescent melanocytes alter the transcriptome and composition of the hair stem cells. The transcriptome is the set of all RNA molecules in a cell, and it is crucial for regulating various cellular functions.
The activation and the changes in the transcriptome and composition of hair stem cells caused by senescent melanocytes result in a significant enhancement of hair renewal. This finding indicates that the senescent melanocytes are sending signals to the hair stem cells, altering their normal behavior. The signals, in turn, encouraged the hair stem cells to exit their quiescent state, which is a state of inactivity, and enter a state of hyperactivity which substantially enhanced hair renewal.
Specifically, it seems that senescent melanocytes produce large quantities of a signaling molecule called osteopontin. This molecule interacts with a receptor on hair stem cells known as CD44. Through this interaction, the normally dormant hair stem cells are stimulated to activate and initiate the growth of hair. It is significant to note that while senescent cells are often associated with the aging process and are generally considered to be detrimental to cellular regeneration, this discovery reveals a beneficial aspect of senescent melanocytes in promoting hair growth. The finding that osteopontin from senescent melanocytes can stimulate hair stem cells might have implications for developing new therapeutic approaches to conditions like hair loss.
The study raises a number of intriguing questions, which warrant further investigation beyond the work presented in the publication. It points out that not all melanocytic nevi (skin moles) in people are hairy, suggesting that certain conditions must be fulfilled for the growth-promoting effect of senescent cells to take place. The study anticipates that comparing hairy and non-hairy human nevi could unravel new cellular and molecular diversities. This should also provide new information on cell signalling that is important in hair stem cell activation. In addition, in their mouse model studies, the author observed that melanocytes became senescent next to hair follicles, but not within the hair follicles themselves. This implies that there is a unique signaling environment within hair follicles that may counteract the oncogene-induced senescence mechanism. Future research could focus on comparing the signals that melanocytes receive in different locations to identify new pathways that prevent senescence. This might be important for understanding grey hair and how to prevent it. Lastly, the authors note that melanocytes are not usually critical regulators of hair follicle stem cells and hair growth timing. However, it seems that when melanocytes acquire senescence, they gain novel properties that resemble those of niche cells. This probably also applies to other niche cells such as dermal papilla cells in hair follicles.
In summary, this research shows that senescent melanocytes can play a crucial role in hair growth by influencing the activity of hair stem cells. Through niche signalling, senescent melanocytes in the skin can cause hair stem cells to exit their inactive state and undergo changes that potentiate hair renewal. This discovery has potential implications for understanding hair growth mechanisms, and possibly for the development of therapies for hair growth disorders​.
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