Most people gradually lose their original hair color as they age. The reason for this is that with age, there are fewer and fewer melanocytes that produce pigments for our hair. A study now shows that the stem cells that produce these melanocytes are amazingly flexible: They can migrate inside a hair follicle and not only develop from an immature to a mature state, but also the other way around. But with age, this ability to regenerate is lost – and our hair turns gray.
Our hair color comes about because pigment-producing cells, the so-called melanocytes, produce pigments in the hair follicles, which are stored in the growing hair. Melanocytes arise from the stem cells of melanocytes. It was previously assumed that these stem cells form a persistent reservoir in the hair follicle, where individual cells develop into mature melanocytes and migrate to the hair growth zone.
Mouse fur growth is observed
However, a new study shows that the process is more complex than previously thought. A team led by Qi Sun of New York University showed in mice that melanocyte stem cells are very flexible as they develop: “Our results show that most melanocyte stem cells move between an undifferentiated stem cell stage and an intermediate stage, the so-called transitory amplification-switch state,” the team reports. . On the other hand, it is known that stem cells are able to develop into mature progeny from a state of transient amplification. On the other hand, they can also develop back into undifferentiated stem cells for self-renewal – a previously unknown mechanism.
For two years, Sun and her colleagues observed how melanocyte stem cells behaved in the hair follicles of mice. To do this, they labeled individual melanocyte stem cells with fluorescence markers so that they could track these stem cells and their offspring under a fluorescence microscope. In this way, they demonstrated that the stem cell reservoir is not in any way spatially separated from the differentiated melanocytes, as previously assumed, but that the stem cells also migrate within the hair follicle. At different locations within the follicle, they are exposed to different protein signals from their environment. These control whether stem cells develop from the intermediate stage into fully differentiated pigment cells or revert to an undifferentiated state.
When stem cells “get stuck”.
Over the course of a lifetime, aging hair continues to fall out and is replaced by new hair. Over time, through this natural process, more and more stem cells are “attached” to a position in the hair follicle where they do not mature and migrate back to the original primary space where they receive the protein signals needed for regeneration. As a result, these cells become unable to regenerate or mature into functional pigment cells. If researchers alter available signaling proteins or accelerate aging by repeatedly plucking hairs from mice, the number of “stuck” stem cells increases and the mice’s original black fur turns gray faster.
“Our study adds to our basic understanding of how melanocyte stem cells function in hair colouring,” says Sun. “The newly discovered mechanisms suggest that the same site of melanocyte stem cells also exists in humans. If this is the case, this represents a potential way to reverse or prevent graying of human hair by helping the engorged cells move back between the developing parts of the hair follicle.”
Gray hair against cancer?
However, the findings are not only helpful in the search for treatments against graying of hair. Because melanocytes are not only responsible for the color of our hair, but also for the pigmentation of our skin. When these cells break down, melanoma, the deadliest form of skin cancer, can develop. “Melanocyte-derived tumors, melanomas, regardless of their fully differentiated pigmented phenotype, retain the ability to self-renew, which is not the case in many other tumors,” Sun and her team explain. “This is why skin cancer is so hard to fight.”
The new findings suggest that the extraordinary ability of melanomas to regenerate could be based on the normal plasticity of melanocyte stem cells. They also offer an explanation for why “stuck” melanocytes are evolutionarily advantageous—even if they’re associated with gray hair: “If the cells stop reproducing, they can’t acquire the mutations that lead to cancer,” explain Carlos Galvan and William Lowry of the University of California. , Los Angeles in a commentary accompanying the study, also published in Nature. “Thus, premature senescence of melanocyte stem cells could be an evolutionary strategy to prevent the development of melanoma.”
Source: Qi Sun (NYU Grossman School of Medicine, NY) et al., Nature, Available Here. doi: 10.1038/s41586-023-05960-6
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