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19 de April, 2023
Study Links "Trapped" Stem Cells with the Appearance of White Hair

A new study led by researchers at the NYU Grossman School of Medicine has revealed that certain stem cells possess the unique ability to move between growth compartments in hair follicles, but get “stuck” as people age, thus losing the ability to mature and maintain hair color.

The study focused on cells present in the skin of mice and also found in humans, called melanocyte stem cells or McSCs. Hair color is controlled by the signal that the pools of non-functional but constantly multiplying McSCs within the hair follicles receive to become mature cells that produce the protein pigments responsible for the color.

Published in the journal Nature on April 19, the new study demonstrated that MCSCs are incredibly plastic. This means that during normal hair growth, these cells move continuously along the maturity axis as they transit between the developing compartments of the hair follicle. It is within these compartments that MCSCs are exposed to different levels of protein signals that influence maturity.

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

The researchers noted that as hair ages, falls out and grows repeatedly, an increasing number of McSCs get “stuck” in the stem cell compartment called the hair bulb. There they remain, do not mature to the state of transient amplification, and do not return to their original location in the germ compartment, where WNT proteins would propel them to regenerate into pigment cells.

“Our study contributes to our basic understanding of how melanocyte stem cells function in hair coloring,” said the study’s principal investigator, Qi Sun, PhD, a postdoctoral researcher at NYU Langone Health. “The newly discovered mechanisms raise the possibility that the same fixation of melanocyte stem cells may exist in humans. If so, this presents a potential pathway to reverse or prevent the whitening of human hair by helping trapped cells move again between the developing compartments of the hair follicle.”

The researchers claim that the plasticity of MCSCs is not present in other self-regenerative stem cells, such as those that make up the hair follicle itself, which are known to move only in one direction along an established timeline as they mature. For example, hair follicle cells in transient amplification never return to their original stem cell state. This helps explain, in part, why hair can continue to grow even when pigmentation fails, Dr. Sun says.

Previous work by the same research team at the NYU Grossman School of Medicine demonstrated that the WNT signal was needed to stimulate McSCs to mature and produce pigment. That study also showed that McSCs were exposed to WNT signaling signals many trillions of times less in the hair follicle hair bulb than in the germinal compartment, which is situated directly below the bulb.

In the most recent experiments on rats, whose hair was physically aged by forced plucking and regeneration, the number of hair follicles with McSCs lodged in the hair bulb increased from 15% before start-up to almost half after forced aging. These cells remained unable to regenerate or mature into pigment-producing melanocytes.

The trapped MCSCs, the researchers found, disrupted their regenerative behavior as they ceased to be exposed to significant WNT signaling signals and therefore lost their ability to produce pigment in new hair follicles, which continued to grow.

On the other hand, other MCSCs that continued to move between the hair bulb and the germ compartment of the hair retained their ability to regenerate as melanocyte stem cells, matured into melanocytes, and produced pigment throughout the two-year study period.

“The loss of chameleon function in melanocyte stem cells may be responsible for whitening and hair color loss,” said study principal investigator Mayumi Ito, PhD, a professor in the Ronald O. Perelman Department of Dermatology and the Department of Cell Biology at NYU Langone Health.

“These results suggest that the mobility of melanocyte stem cells and their reversible differentiation are key to keeping hair healthy and colorful,” said Dr. Ito.

Dr Ito says the team has plans to investigate ways to restore the mobility of the MCSCs or physically move them back to their germinal compartment, where they can produce pigment.

For the study, the researchers used recent 3D intravital imaging and scRNA-seq techniques to track the cells in near real-time as they aged and moved within each hair follicle.

The study was funded by grants from the U.S. National Institutes of Health P30CA016087, S10OD021747, R01AR059768, R01AR074995, and U54CA263001, as well as Department of Defense grants W81XWH2110435 and W81XWH2110510.

In addition to Dr. Sun and Dr. Ito, other NYU Langone researchers involved in this study are co-investigators Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, Michael Cammer, and Denise Gay. Other co-investigators of the study are M. Mark Taketo of Kyoto University in Japan and Sarah Millar of the Icahn School of Medicine at Mount Sinai in New York City.

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