Research finds that ‘stuck’ stem cells are involved in graying of hair

C.A new study shows that some stem cells have the unique ability to move between growth compartments in hair follicles, but with age they become immobile and lose the ability to mature and maintain hair color.

The new study, led by researchers at New York University’s Grossman School of Medicine, focused on cells in the skin of mice, which are also present in humans, called melanocyte stem cells (McSCs). Hair color is controlled by whether a non-functioning but continuously proliferating pool of McSCs within the hair follicle receives signals to become mature cells that make the protein pigments responsible for color. .

It was published in the magazine Nature A new study published online on April 19 showed that McSCs are remarkably plastic. This means that during normal hair growth, such cells continuously move back and forth along the maturation axis as they pass between compartments of the developing follicle. It is inside these compartments that McSCs are exposed to different levels of protein signals that influence maturation.

Specifically, the research team found that McSCs changed between the most primitive stem cell state and the next stage of maturation, the passage amplification state, depending on their location.

The researchers found that as hair ages, sheds, and regrows, the number of McSCs that fill a stem cell compartment called the follicle bulge increases. They remain there, do not mature to the passage-amplifying state, and do not return to their original position within the germinal compartment where WNT proteins must have encouraged regeneration into pigment cells.

“Our study furthers our fundamental understanding of how melanocyte stem cells function to color hair,” said Qi, principal investigator and postdoctoral fellow at New York University Langone Health. Dr. Sun said. “The newly discovered mechanism raises the possibility that the same fixed location of melanocyte stem cells also exists in humans. If so, it allows the clogged cells to move again between the developing hair follicle compartments.” This presents a potential pathway to reverse or prevent graying of human hair.”

McSC plasticity is not present in other self-renewing stem cells that make up the hair follicle itself, which are known to migrate in only one direction along established timelines as they mature, the researchers said. . For example, transport-amplifying hair follicle cells never revert to their original stem cell state. This helps explain, in part, why hair continues to grow even when pigmentation fails, Dr. Sun says.

Previous work by the same research team at New York University Grossman School of Medicine showed that WNT signaling is required to stimulate McSCs to mature and produce pigment. The study also showed that McSCs were trillions of times less exposed to her WNT signaling within the bulge of the hair follicle than in the hair germinal compartment located directly beneath the bulge.

A recent experiment using mice whose hair was physically aged by plucking and forced regrowth found that the number of hair follicles with McSCs lodged in the bulge of the follicle was 15 before plucking. increased from a percent to nearly half after forced aging. These cells remained unable to regenerate or mature into pigment-producing melanocytes.

The researchers found that the stalled McSCs became less exposed to WNT signaling and thus stopped their regenerative behavior and, consequently, 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 germ retained the ability to regenerate as McSCs, mature into melanocytes, and generate pigment over the entire two-year study period. I was.

“The cause of gray hair and hair color loss may be the loss of chameleon-like function of melanocyte stem cells,” said lead researcher Ronald O. Perelman, Mayumi Ito, professor of dermatology and medicine. said Dr. Cell Biology, New York University Langone Health.

“These findings suggest that melanocyte stem cell motility and reversible differentiation are key to maintaining hair health and color,” said Dr. Ito.

Dr. Ito said the research team plans to study ways to restore the motility of the McSCs or to physically return them to the embryonic compartment where they can produce pigment.

In this study, researchers used state-of-the-art 3D in vivo imaging and scRNA-seq technology to track in near real-time how cells age and migrate within each hair follicle.

Funding for this study was provided by National Institutes of Health grants P30CA016087, S10OD021747, R01AR059768, R01AR074995, and U54CA263001. The Department of Defense has licensed her W81XWH2110435 and W81XWH2110510.

In addition to Dr. Sun and Dr. Ito, researchers from the University of New York University of Langone involved in the study include collaborators Wendy Lee, Hai Fu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Che・Ho Lim, Makoto Takeo, Michael Cummer, and Dennis Gay. . Other research collaborators are M. Mark Taketo of Kyoto University, Japan, and Sarah Miller of Icahn School of Medicine, Mount Sinai, New York City.

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