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Why Does Hair Turn Gray? Research Uncovers Role of “Stuck” Stem Cells
A study by NYU Grossman School of Medicine researchers found that melanocyte stem cells (McSCs) lose their ability to move between hair follicle compartments as people age, leading to hair graying. Restoring McSC motility or moving them back to their germ compartment could potentially reverse or prevent hair graying in humans.
Certain stem cells have a unique ability to move between growth compartments in hair follicles, but get stuck as people age and so lose their ability to mature and maintain hair color, a new study shows.
Led by researchers from NYU Grossman School of Medicine, the new work focused on cells in the skin of mice and also found in humans called melanocyte stem cells, or McSCs. Hair color is controlled by whether nonfunctional but continually multiplying pools of McSCs within hair follicles get the signal to become mature cells that make the protein pigments responsible for color.
Publishing in the journal Nature on April 19, the new study showed that McSCs are remarkably plastic. This means that during normal hair growth, such cells continually move back and forth on the maturity axis as they transit between compartments of the developing hair follicle. It is inside these compartments where McSCs are exposed to different levels of maturity-influencing protein signals.
Specifically, the research team found that McSCs transform between their most primitive stem cell state and the next stage of their maturation, the transit-amplifying state, and depending on their location.
The researchers found that as hair ages, sheds, and then repeatedly grows back, increasing numbers of McSCs get stuck in the stem cell compartment called the hair follicle bulge. There, they remain, do not mature into the transit-amplifying state, and do not travel back to their original location in the germ compartment, where WNT proteins would have prodded them to regenerate into pigment cells.
“Our study adds to our basic understanding of how melanocyte stem cells work to color hair,” said study lead investigator Qi Sun, PhD, a postdoctoral fellow at NYU Langone Health. “The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans. If so, it presents a potential pathway for reversing or preventing the graying of human hair by helping jammed cells to move again between developing hair follicle compartments.”
Researchers say McSC plasticity is not present in other self-regenerating stem cells, such as those making up the hair follicle itself, which are known to move in only one direction along an established timeline as they mature. For example, transit-amplifying hair follicle cells never revert to their original stem cell state. This helps explain in part why hair can keep growing even while its pigmentation fails, says Sun.
Earlier work by the same research team at NYU showed that WNT signaling was needed to stimulate the McSCs to mature and produce pigment. That study had also shown that McSCs were many trillions of times less exposed to WNT signaling in the hair follicle bulge than in the hair germ compartment, which is situated directly below the bulge.
In the latest experiments in mice whose hair was physically aged by plucking and forced regrowth, the number of hair follicles with McSCs lodged in the follicle bulge increased from 15% before plucking to nearly half after forced aging. These cells remained incapable of regenerating or maturing into pigment-producing melanocytes.
The stuck McSCs, the researchers found, ceased their regenerative behavior as they were no longer exposed to much WNT signaling and hence their ability to produce pigment in new hair follicles, which continued to grow.
By contrast, other McSCs that continued to move back and forth between the follicle bulge and hair germ retained their ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire study period of two years.
“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” said study senior 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 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 the Department of Cell Biology at NYU Langone.
Ito says the team has plans to investigate means of restoring motility of McSCs or of physically moving them back to their germ compartment, where they can produce pigment.
For the study, researchers used recent 3D-intravital-imaging and scRNA-seq techniques to track cells in almost real time as they aged and moved within each hair follicle.
注释：
Melanocyte：n
表示" [医]黑素细胞"，means "a cell in the basal layer of the epidermis that produces melanin under the control of the melanocyte-stimulating hormone"，如：This substance not only stimulates the sensitivity of Melanocyte but also protects our skin from sunburn. 该物质不仅能够刺激黑素细胞的敏感度，而且可以保护我们的皮肤受到太阳灼伤。
follicle: n
表示" 小囊；卵泡；滤泡"，means "any small spherical group of cells containing a cavity"，如：Sebaceous glands are attached to each hair follicle. 皮脂腺附着于每个毛囊上。
compartment: n
表示" 间隔；"，means " any of the sections into which a larger area or enclosed space"，如：This is a case with separate compartments for shoes, jewelry, etc. 这是一个分格存放鞋、珠宝等的箱子。
pigment: n
表示" 色素；"，means "dry coloring material (especially a powder to be mixed with a liquid to produce paint, etc.)"，如：This pigment is a good common food additive. 该色素是稳定性好的食品添加剂。
amplify: v
表示" 扩大；增强"，means "increase in size, volume or significance"，如：We must amplify our effort by working a lot harder. 我们必须更努力地工作来扩大成果。
bulge: v; n
表示" 膨胀；"，means "swell or curve outwards;a swelling of a surface caused by pressure from inside or below"，如：My pockets were bulging with apples. 我的口袋因装着苹果而鼓起来了。The apple made a bulge in his pocket. 苹果把他口袋塞得鼓了起来。
prod: v; n
表示" 戳；刺；刺激"，means "to push against gently;poke or thrust abruptly"，如：He prodded at the pig with his walking-stick. 他用手杖戳那口猪。She gave the man a prod with her umbrella.她用伞捅了那男子一下。
pigmentation: n
表示" 染色；着色"，means "coloration of living tissues by pigment"，如：The doctor said permanent dermal pigmentation is a form of microsurgery. 医生说永久的皮肤染色是一种显微手术。
pluck: v
表示"猛拉；拔；"，means " pull (the feathers) off;pick; pull"，如：A stranger plucked at my sleeve as I was leaving.我刚要离去，一个陌生人拽我的袖子。He plucked a rose for his lover. 他为情人摘了一朵玫瑰花。
lodge: v
表示" 存放；临时住宿；"，means " supply sb with a room or place to sleep in for a time"，如：You can lodge the valuables in the bank. 你可以把贵重物品存放在银行里。I lodged at a friend's house. 我寄住在一个朋友家里。
germ：n
表示" 细菌; 胚芽"，means "very small living thing which is harmful"，如：Germs may invade the organism. 细菌会侵入有机体。This beetle eats mainly the germ of the grain. 这种甲虫主要吃谷物的胚芽。
retain：v
表示" 保持；保留"，means "hold back within;"，如：His speech could not retain the interest of his audience. 他的讲话不能保持住听众的兴趣
chameleon: n
表示" 变色龙；"，如：The chameleon can take on the colours of its background. 变色龙可将身体颜色变得与周围环境相同。
motility: n
表示" 运动性；自动力"，means "ability to move spontaneously and independently"，如：All of these cells exhibit motility. 所有这些细胞均表现移动性。
differentiation: n
表示" 区别；分化"，means "a discrimination between things as different and distinct"，如：There is no differentiation without contrast.没有比较就看不出区别。
中文简要说明：
人上了年纪，或者压力与情绪低落，都可能出现白头发，杜甫有诗「白头搔更短，浑欲不胜簪」就是形容苦闷的心情。科学家在最近终于找到生理上的原因，也就有可能逆转过程，使头发再现颜色.
每日科学(ScitechDaily)报导，毛发的生成有些复杂，首先它需要有毛囊细胞(hair follicle)，它会持续滋生，成为毛发。但是这样生成的毛发是没有颜色的，还需要帮头发填充颜色的黑素细胞(melanocyte)，黑素细胞会生成黑色素，渗入毛囊细胞后，成长的毛发才会有颜色。
另一方面，毛囊细胞的前身是毛囊干细胞(hair follicle stem cells，HFSCs)；黑素细胞的前身是黑素细胞干细胞(melanocyte stem cells,McSCs)，要是McSCs失去在毛囊生长室之间移动的能力，就会来不及为头发染色，导致头发变白。因此，只要恢复 McSC 的活力，或将它们移回毛囊生长室，就可能逆转过程。纽约大学格罗斯曼医学院(NYU Robert I. Grossman School of Medicine)的研究团队以小鼠为实验，知晓了整个毛发生长的过程，并在 4 月 19 日发表在《自然》杂志上。
具体而言，研究小组发现，McSCs 必须在毛囊生长室不断游移，才能持续为头发染色，而头发本身是有寿命的，会老化、脱落，然后反复重新长出，这使得越来越多的 McSC 会失去活力，卡在称为毛囊隆起位(hair follicle bulge)的干细胞区室中，它们留在那里，不会成熟为黑素细胞，也不会返回它们的原始位置，因此就失去为头发染色的作用。
研究人员表示，毛囊胞需要 WNT 信号，来刺激 McSC 成熟并产生色素。一旦它们卡在毛囊隆起位，信号值就会低上数亿倍，毛囊收不到染色的信号，自然也就白了。
所以，现在研究人员要寻找如何让黑素细胞干细胞恢复运动活力的办法，或者将它们移回它们的培养室，在那里它们可以产生色素。或许有一天，就能阻止头发持续变白，甚至逆转这一过程。
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