Highlights in this article:
Discovering a groundbreaking mechanism in melanocyte stem cells (McSCs), Dr. Ito’s group has revealed that these cells can toggle between self-renewal and differentiation states, defying the conventional understanding of stem cell behavior. This new model, driven by local microenvironmental cues, could pave the way for innovative strategies to prevent hair greying by modulating McSC mobility and dedifferentiation.
Background:
Hair greying is a common and natural sign of aging, resulting from a decrease in the production of melanin, the pigment responsible for hair color. Several mechanisms contribute to hair greying with age:
- Melanocyte stem cell (McSC) depletion: Melanocytes are specialized pigment-producing cells found in hair follicles. Melanocyte stem cells are responsible for maintaining the melanocyte population throughout the hair growth cycle. With aging, the number of McSCs decreases, leading to a reduced ability to replenish lost melanocytes and subsequently less pigment production.
- Decline in melanocyte function: As a person ages, the functionality of melanocytes may decline, leading to reduced melanin production. This decrease in pigment synthesis can result in hair becoming progressively greyer over time.
- Oxidative stress: Oxidative stress occurs when the balance between the production of reactive oxygen species (free radicals) and the body’s ability to neutralize them is disrupted. Accumulation of oxidative damage can negatively impact melanocytes and their ability to produce melanin. Increased oxidative stress is associated with aging and can contribute to hair greying.
- Genetic factors: Hair greying has a genetic component, with some individuals predisposed to grey hair earlier than others due to their genetic makeup. Specific genes, such as IRF4, have been linked to the regulation of hair color and the onset of hair greying.
- Hormonal changes: Hormones play a role in hair pigmentation, and age-related hormonal changes can contribute to hair greying. For example, decreased levels of hormones like estrogen, progesterone, and melanocyte-stimulating hormone can influence melanocyte function and melanin production.
However, the reason behind the melanocyte stem cell (McSC) system failing earlier than other adult stem cell populations remains unclear. Understanding the mechanisms of hair greying with age can help us develop strategies to prevent or delay the onset of greying, but it is essential to note that hair greying is a natural part of the aging process and occurs in varying degrees for different individuals.
Discovery:
Dr. Ito’s group has unveiled a new model of melanocyte stem cell (McSC) maintenance that underscores a previously unknown level of plasticity within the hair follicle. This discovery has significant implications for understanding hair greying and melanoma treatment, making it an essential topic for those interested in the biology of aging and skin cancer research. The innovative model showcases how McSCs can act as both stem cells and transit-amplifying (TA) cells during the onset of regeneration, demonstrating their chameleon-like ability to change their phenotype depending on their location within the hair follicle. Proper localization of McSCs is crucial for preventing hair greying, a common concern among individuals as they age.
As hair follicles age, the movement of McSCs between stem cell and TA compartments becomes less precise, leading to an accumulation of McSCs that fail to undergo the required movement to generate new melanocytes, the pigment-producing cells responsible for hair color. Understanding the biology of hair greying could pave the way for the development of innovative strategies to prevent or delay this natural aging process, attracting widespread interest from those seeking to maintain their natural hair color for as long as possible.
Furthermore, they have implications for the treatment of melanoma, a highly dangerous and aggressive form of skin cancer derived from melanocytes. The plastic nature of normal melanocytes under physiological conditions could partially explain the unique challenges associated with treating melanoma. Melanoma cells, unlike many other types of cancer cells, retain their self-renewal ability regardless of their fully differentiated, pigmented phenotype. Understanding the plasticity of melanocyte stem cells can potentially contribute to advancements in melanoma research and treatment, helping to develop more effective therapies for this aggressive form of skin cancer. These insights could generate significant interest from those involved in the field of dermatology, oncology, and skin cancer research.
In summary, Dr. Ito’s group has provided valuable insights into the dynamic behavior of melanocyte stem cells, highlighting the importance of their localization within the hair follicle and the implications for both hair greying prevention and melanoma research. Further exploration of these findings could lead to the development of novel approaches for preventing hair greying and improving melanoma treatment outcomes, capturing the attention of those interested in aging and skin cancer research.
For more information:
Nature 2023 4/19
https://www.nature.com/articles/s41586-023-05960-6
Dedifferentiation maintains melanocyte stem cells in a dynamic niche
Dr. Ito’s website: