Mouse hair turns gray when certain stem cells get stuck

Hair might go gray when stem cells with wanderlust have their travels interrupted.

Stem cells involved in making the pigment that gives hair its color behave much differently than other stem cells do, researchers report April 19 in Nature. Rather than staying put, these melanocyte stem cells travel up and down hair follicles all while oscillating between two different forms of maturity. But it’s not the unusual behavior that leads to graying. It’s when these stem cells stop their quirky ways that hair turns white.

That movement is really strange behavior for stem cells, says William Lowry, a hair follicle biologist at UCLA. Stem cells usually settle into a niche, or compartment, dividing when they need to, he says. “Their progeny go off and do interesting things … whereas the stem cells typically stay put.” Lowry was not involved in the study but coauthored a commentary about the work that also appeared April 19 in Nature.

Stem cells are immature cells that make more of themselves and give rise to cells that will mature to perform specific tasks. Melanocyte stem cells can become melanocytes, the cells that make pigments which give hair and skin their color.  

Qi Sun and Mayumi Ito Suzuki, stem cell biologists at New York University Grossman School of Medicine, didn’t set out to study gray hair. They wanted to know how melanocyte stem cells in the hair follicle behave. The researchers had previously implicated such cells in melanoma skin cancer.    

To understand the life cycle of melanocyte stem cells, Sun watched the same patch of hair follicles on a mouse again and again over the mouse’s lifetime. She saw that melanocyte stem cells move out of a compartment at the base of the follicle and up into the follicle bulge. Then the cells turn around and head back to the base.

That is not the cells’ only odd behavior. The stem cells mature, or differentiate, into an intermediate form that ultimately gives rise to melanocytes, the cells that make the pigment melanin, which colors hair. For other stem cells, once they start maturing there is no going back. But melanocyte stem cells can toggle between the less-mature and more-mature states.

Being able to slide between the two states is necessary for hair to keep its color, Sun and colleagues report. The intermediate state is needed for migration to the base of the growing hair shaft, where some of the cells develop into melanocytes to color the hair. And the stem cell state regenerates a pool of stem cells that can then mature to touch up the roots.

The stem cells must move because proteins that help control cell maturity and proliferation are found in different compartments of the hair follicle. A protein called WNT made by cells in the compartment at the base of the follicle causes stem cells to mature into melanocytes, the researchers found. But too much WNT activity prevented the stem cells from sliding back into their regenerative state.

As mice aged, or if the researchers plucked hairs to make them grow faster, more and more worn-out melanocyte stem cells got stuck in the hair follicle bulge. There they couldn’t mature into the intermediate stage to travel back to the base compartment where they could have formed melanocytes. That led to depletion of the color-producing cells, causing the hair to turn gray.

The graying could be reversed though. Getting the cells moving and starting the maturation cycle again gave hair back its color, the team found. Previous research has shown that periods of stress deplete melanocytes and temporarily cause hair to gray (SN: 1/23/20; SN: 6/11/09).

In principle, this sort of behavior from melanocyte stem cells may cause humans’ hair to turn gray too, says Rui Yi, a stem cell biologist at Northwestern University Feinberg School of Medicine in Chicago, who was not involved in the research. Until researchers can observe human hair follicles over time, he says, it’s not possible to say for sure.