Most people gradually lose their original hair color as they age. The reason for this is that with increasing age there are fewer and fewer melanocytes that produce the pigments for our hair. A study now shows that the stem cells that give rise to these pigment-producing cells are amazingly flexible: They can migrate within the hair follicle and not only develop from an immature to a mature state, but also in the other direction. With age, however, this ability to renew is lost – and our hair turns gray.
Our hair color comes about because pigment-producing cells, the so-called melanocytes, produce dyes in our hair follicles, which are stored in the growing hair. Melanocytes arise from melanocyte stem cells. It was previously assumed that these stem cells form a fixed reservoir in the hair follicles, from which individual cells develop into mature melanocytes and migrate to the hair growth zone.
Mouse fur observed growing
However, a new study shows that the process is more complex than previously thought. A team led by Qi Sun from New York University demonstrated in mice that melanocyte stem cells are extraordinarily flexible during their development: “Our results show that most melanocyte stem cells move between an undifferentiated stem cell stage and an intermediate stage, the so-called transit amplification status, switch,” reports the team. On the one hand, the stem cells are known to be able to develop into mature offspring from the transit amplification status. 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 the melanocyte stem cells behaved in the hair follicles of mice. To do this, they marked individual melanocyte stem cells with fluorescence markers so that they could track these stem cells and their offspring under the fluorescence microscope. In this way, they proved that the stem cell reservoir is by no means spatially separated from the differentiated melanocytes, as was 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 the stem cells develop from the intermediate stage into fully differentiated melanocytes or back into an undifferentiated state.
When stem cells “get stuck”
Over the course of life, aged hair keeps falling out and is replaced by new ones. Over time, through this natural process, more and more stem cells get “stuck” in a position in the hair follicle where they neither mature nor migrate back to their original core compartment where they would receive the protein signals necessary for renewal. As a result, these cells become unable to regenerate or mature into functional melanocytes. If the researchers varied the available signaling proteins or accelerated aging by repeatedly plucking hair from the mice, the number of “stuck” stem cells increased and the originally black fur of the mice turned gray faster.
“Our study adds to our fundamental understanding of how melanocyte stem cells work in hair coloring,” says Sun. “The newly discovered mechanisms suggest that the same positioning of melanocyte stem cells also exists in humans. If so, this presents a potential way to reverse or prevent human hair graying by helping congested cells move back between the developing hair follicle compartments.”
Gray hair against cancer?
However, the results can not only help in the search for remedies against graying of the hair. Because melanocytes are not only responsible for our hair color, but also for the pigmentation of our skin. When these cells degenerate, melanoma, the most dangerous form of skin cancer, can develop. “The 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,” explain Sun and her team. “That’s why melanoma is so hard to fight.”
The new results indicate that the extraordinary ability of melanoma to regenerate could be based on the natural plasticity of the melanocyte stem cells. They also provide an explanation as to why melanocyte “getting stuck” might have been evolutionarily advantageous – even if it is associated with gray hair: “If the cells stop replicating, they cannot 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 the journal Nature. “Thus, the premature aging of melanocyte stem cells could be an evolutionary strategy to prevent the development of melanoma.”
Source: Qi Sun (NYU Grossman School of Medicine, New York) et al., Nature, doi: 10.1038/s41586-023-05960-6