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Aging melanocyte stem cells and gray hair

The findings suggest why hair may gray with age. Adobe Stock

Melanocytes are the cells that produce the pigment responsible for skin and hair color. They arise from melanocyte stem cells (McSCs). McSCs fail earlier than the hair follicle stem cells responsible for hair growth, leading to hair graying with age. What causes this early McSC failure remains unknown.

McSCs are thought to behave much like hair follicle stem cells. Hair follicle stem cells live in a part of the hair follicle known as the bulge. They produce progenitor cells that populate an area called the hair germ. During hair growth, the progenitor cells differentiate (develop) into mature cells. Meanwhile, the original stem cells remain as stem cells, separate from the progenitors. This progression from stem to progenitor to mature cells goes only one way.

An NIH-funded team of researchers, led by Dr. Mayumi Ito at New York University, investigated whether McSCs behave in the same way. The researchers studied mice that were engineered to have fluorescent McSCs in their hair follicles. They could thus follow the McSCs throughout the hair growth cycle under a microscope. Their findings appeared in Nature on April 19, 2023.

The scientists found that McSCs that started in the hair germ had one of two fates. Some gave rise to mature melanocytes at the base of the growing hair. These died once the hair growth finished. Other McSCs migrated up towards the bulge and continued to behave like stem cells.

The team next took a closer look at the cells’ structure and gene activity at different stages of hair growth. This revealed that when hair growth began, all the McSCs in the hair germ began differentiating so that they were partway to becoming melanocytes. Unlike HFSCs, there was no separate pool of McSCs that never differentiated.

Those that migrated up to the bulge, the team found, “dedifferentiated” back into stem cells. Even highly differentiated, pigment-producing McSCs could dedifferentiate into stem cells.

The team discovered that McSC differentiation was triggered in the hair germ by molecular signals from nearby cells. But in the bulge region, these signals were suppressed. Many, but not all, McSCs that migrated to the bulge migrated back to the hair germ compartment at the end of the growth cycle. There, they could participate in the next round of growth. Those that stayed in the bulge couldn't make new pigment-producing cells. Moving between the bulge and the hair germ, then, allowed the McSCs to switch between differentiating and stem cell states.

The researchers observed that as the hair follicles aged in older mice, more and more McSCs stayed put in the region between bulge and hair germ. These could not become either new mature melanocytes for pigmentation or functional McSCs for later rounds of hair pigmentation.

The authors postulate that these ‘stuck’ cells may help explain hair graying in older individuals. “It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” Ito says.

The findings also suggest that if this McSC movement could be restored, it might prevent or reverse hair graying.

—by Brian Doctrow, Ph.D.