A recent study conducted by researchers from NYU Grossman School of Medicine discovered that certain stem cells in the skin of mice and humans, called melanocyte stem cells or McSCs, possess the unique ability to move between growth compartments within hair follicles. These cells are responsible for maintaining hair color by producing protein pigments. However, the study found that as people age, these cells get stuck and lose their ability to mature and maintain hair color. The study, published in the journal Nature on April 19, showed that McSCs are highly adaptable and constantly move back and forth between maturity levels in different compartments of the developing hair follicle, where they are exposed to different levels of protein signals that affect their maturity.
The research team has discovered that McSCs, which are primitive stem cells, can transform into the transit-amplifying state, which is a more developed stage of maturation, based on where they are located. Specifically, the team found that McSCs can switch between these two states depending on their location.
As hair goes through the natural process of aging, shedding, and regrowing, more and more McSCs become trapped in a stem cell compartment called the hair follicle bulge. These cells are unable to mature into the transit-amplifying state and do not return to their original location in the germ compartment, where WNT proteins would have triggered them to regenerate into pigment cells.
According to study lead investigator Qi Sun, this study enhances our understanding of how melanocyte stem cells contribute to hair color. The new mechanisms uncovered in the study suggest that the same phenomenon of fixed-positioning of melanocyte stem cells may occur in humans. If this is the case, it could open up new possibilities for preventing or reversing gray hair by helping these trapped cells move between different hair follicle compartments during development.
According to a new study, researchers have discovered that melanocyte stem cells (McSCs) possess a unique characteristic of being plastic, which is absent in other stem cells that make up the hair follicle. These cells are known to move back and forth on the maturity axis during normal hair growth, and their exposure to different levels of maturity-influencing protein signals occurs inside the compartments of the developing hair follicle. The researchers also found that the WNT signaling was necessary to stimulate McSCs to mature and produce pigment. The number of hair follicles containing McSCs lodged in the follicle bulge increased from 15% before plucking to almost half after forced aging in mice. However, these cells remained stuck and were incapable of regenerating or maturing into pigment-producing melanocytes.
In contrast, other McSCs that moved back and forth between the follicle bulge and hair germ retained their ability to produce pigment as melanocytes and regenerate as McSCs over the study period of two years. According to Mayumi Ito, the senior investigator of the study, it is the loss of chameleon-like function in melanocyte stem cells that may lead to graying and hair color loss. The findings suggest that the ability of McSCs to move and differentiate reversibly is crucial to maintaining healthy and colored hair.
Ito plans to explore ways to restore McSC motility or move them physically back to their germ compartment, where they can produce pigment. The research team used 3D-intravital-imaging and scRNA-seq techniques to track cells almost in real-time as they aged and moved within each hair follicle.
The study was funded by National Institutes of Health grants P30CA016087, S10OD021747, R01AR059768, R01AR074995, and U54CA263001; and Department of Defense grants W81XWH2110435 and W81XWH2110510. Researchers from NYU Langone who were involved in the study are Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, Michael Cammer, and Denise Gay, while M. Mark Taketo at Kyoto University in Japan and Sarah Millar at Icahn School of Medicine at Mount Sinai in New York City were also co-investigators.