Graying Hair a Result of “Stuck” Stem Cells

A new study by NYU Langone researchers finds that the stem cells required for hair pigmentation can become “stuck”, preventing their differentiation and the maintenance of hair color. The research is published in Nature.

What causes gray hair?

Noticed a few strands of silvery-gray weaving through your once boldly colored locks? Don’t worry, me too.

Contrary to popular belief, our hair doesn’t “turn” gray – i.e., hair strands that are brown, blonde or red do not suddenly lose their color. Rather, hair color is determined by a type of stem cell called melanocyte stem cells, or McSCs, found in the bulge and hair germ area of the hair follicle.  

Stem cells – when prompted – can mature and differentiate into different types of cells found across the human body. When a strand of hair falls out, McSCs receive signals that trigger their maturity into melanocytes, which ultimately migrate into the hair bulb and inject pigment into the hair shaft as the new hair grows.  

The distinct functions and self-renewal capabilities of McSCs have not been well characterized to date. In the new study, Dr. Qi Sun, a postdoctoral fellow at NYU Langone Health, and collaborators sought to better understand the hierarchical structure of the McSC system.

“Stuck” stem cells cannot continue to mature

Sun and team used 3D imaging and single-cell RNA sequencing to track McSC cells in mice as they aged and moved within hair follicles during a two-year study. The researchers say they were surprised to discover that these stem cells are incredibly plastic. They demonstrate “chameleon-like” features, whereby their phenotype (i.e., state of differentiation) is flexible depending on which compartment of the hair follicle they are in, and therefore which protein signals they are subjected to.

The location of the stem cells is key for determining whether McSCs transform from a primitive stem cell state to their next phase of maturation, called the transit-amplifying state. As aging occurs, hair strands fall out and regrow, repeatedly. The researchers modeled this process by physically plucking the hair of mice and monitoring the movement of McSCs. They found that forced aging through plucking resulted in a growing number of McSCs becoming “stuck” in a particular compartment of the hair follicle, the bulge. The number of cells “jammed” in this region increased from 15% before plucking to almost 50% after plucking.

Sun and colleagues found that the McSCs stuck in this compartment are prohibited from maturing into the transit-amplifying state, but they also cannot return back to their original location – the germ compartment – where a milieu of signaling proteins might have prompted them to regenerate into pigment cells. This process is associated with graying hair.

Hair-coloring stem cells (at left, in pink) need to be in the hair germ compartment in order to be activated (at right) to develop into pigment. Credit: Courtesy of Springer-Nature Publishing or the journal Nature. 

Could this system be manipulated?

“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” says senior investigator of the study Dr. Mayumi Ito, 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,” adds Ito.

“Our study adds to our basic understanding of how melanocyte stem cells work to color hair,” says Sun. “The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans.” If the research translates, there could be opportunities to intervene with hair graying by helping the “jammed” cells to move between the hair follicle compartments once again, the researchers emphasize.

Reference: Sun Q, Lee W, Ogawa T et al. De-differentiation maintains melanocyte stem cells in a dynamic niche. Nature. 2023. doi: 10.1038/s41586-023-05960-6

This article is a rework of a press release issued by NYU Langone Health. Material has been edited for length and content.