A study by researchers at the NYU Grossman School of Medicine reveals that melanocyte stem cells (McSCs), which are essential for maintaining hair color, lose their ability to move between growth compartments of hair follicles with age. I was. This loss of mobility causes gray hair. McSC is plastic. That is, it constantly changes between maturation stages and compartments within the hair follicle. However, with repeated hair aging and regrowth, more of her McSCs become trapped in the bulge of the hair follicle and unable to mature into pigment-producing cells. Researchers believe that restoring McSC motility or returning them to the embryonic compartment may reverse or prevent gray hair in humans.
A study by researchers at the NYU Grossman School of Medicine found that melanocyte stem cells (McSCs) lose the ability to move between hair follicle compartments as we age, leading to gray hair. Restoring McSC motility or returning them to the embryonic compartment may reverse or prevent gray hair in humans.
Certain stem cells have the unique ability to move between growth compartments in hair follicles, but as they age they get stuck and lose their ability to mature and maintain hair color, new research shows. I’m here.
The new study, led by researchers at the NYU Grossman School of Medicine, focused on cells in mouse skin that were also found in humans called melanocyte stem cells (McSCs). Hair color depends on whether a non-functional but continuously growing pool of her McSCs within the hair follicle receives signals to become mature cells that make the protein pigments responsible for color. controlled.
Publication in magazines Nature A new study on April 19 showed that McSCs are highly plastic. This means that during normal hair growth, such cells continuously move back and forth on the maturation axis as they migrate between compartments of the growing follicle. It is inside these compartments that are exposed to protein signals that influence the level of maturity.
Specifically, the research team found that McSCs shift between their most primitive stem cell state and the next stage of maturation, a transport-amplifying state, depending on their location.
Hair-pigmenting stem cells (left, pink) must reside in the hair germ compartment in order to be activated and develop into pigment (right).Credit: Courtesy of Springer-Nature Publishing or the journal Nature
Researchers found that as hair ages, sheds, and then regrows, the number of McSCs trapped in a stem cell compartment called the follicle bulge increases. It stays there, does not mature to a passage-amplifying state, and does not return to its original location in the reproductive compartment where the WNT protein prompted its regeneration into a pigment cell.
“Our study adds to our basic understanding of how melanocyte stem cells color hair,” said the study’s principal investigator and postdoctoral fellow at NYU Langone Health. Dr. Qi Sun said. “The newly discovered mechanism raises the possibility that the same fixed arrangement of melanocyte stem cells also exists in humans. By doing so, we present a potential pathway to reverse or prevent graying of human hair.
According to the researchers, McSC plasticity is present in other self-renewing stem cells, such as those that make up the hair follicle itself, which are known to migrate only in one direction along established timelines as they mature. No. For example, passage-amplified hair follicle cells never revert to their original stem cell state. This helps explain part of why hair continues to grow even when pigmentation fails, Sun says.
Previous work by the same research team at NYU showed that WNT signaling is required to stimulate McSCs to mature and produce pigment. That study also showed that her McSCs were exposed to her WNT signal trillions of times less in the bulge of the follicle than in the hair germ compartment located directly beneath the bulge.
In a recent experiment in mice whose hair was physically aged by plucking and forced regrowth, the number of hair follicles with McSCs lodged in the bulge of the follicle was nearly halved after forced aging from 15% before plucking. Increased. These cells failed to regenerate or mature into pigment-producing melanocytes.
Researchers found that stuck McSCs ceased regenerative behavior because they were no longer exposed to WNT signals and lost their ability to produce pigment in new growing hair follicles.
In contrast, other McSCs that continued to shuttle between the bulge of the follicle and the hair bud retained the ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire two-year study period. .
“It’s a loss of chameleon-like function in melanocyte stem cells that may be responsible for gray hair and loss of hair color,” says Ronald O. Perelman, professor of dermatology and academia, senior researcher. Researcher Mayumi Ito, Ph.D. She holds a PhD in Cell Biology from NYU Langone Health.
“These findings suggest that melanocyte stem cell motility and reversible differentiation are key to keeping hair healthy and colored,” said Ito, who is also a professor in NYU Langone’s Department of Cell Biology. said.
Ito said the team plans to investigate ways to restore the motility of the McSCs, or physically return them to the reproductive compartment where they can produce pigment.
In this study, researchers used recent 3D intravital imaging and scRNA-seq technology to track cells in near real-time as they age and migrate within each hair follicle.
Reference: “Dedifferentiation Maintains Melanocyte Stem Cells in a Dynamic Niche,” Qi Sun, Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, Michael Cammer, M. Mark Taketo, Denise L Gay, Sarah E. Miller, Mayumi Ito, April 19, 2023, Nature.
DOI: 10.1038/s41586-023-05960-6
Funding for this study was provided by National Institutes of Health grants P30CA016087, S10OD021747, R01AR059768, R01AR074995, and U54CA263001. The Department of Defense grants W81XWH2110435 and W81XWH2110510.
Besides Sun and Ito, other NYU Langone researchers involved in the study include collaborators Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, and Michael Cammer. , and Denise Gay. Other research collaborators are M. Mark Taketo of Kyoto University in Japan and Sarah Millar of her Icahn School of Medicine in Mount Sinai, New York City.
