Research: Stuck stem cells are connected to ageing of hair

WASHINGTON: Based on a recent study, specific stem cells can travel between growth compartments in hair follicles with a special aptitude, but as people age, they become trapped and lose the capacity to mature and preserve hair colour.

The latest research, led by scientists from NYU Grossman School of Medicine, concentrated on cells called melanocyte stem cells, or McSCs, which are found in both the skin of mice and humans. The signal to mature cells that produce the protein pigments responsible for colour is received by pools of nonfunctional, continuously proliferating McSCs found within hair follicles.

The latest learning, which was published online in the journal Nature Online on April 19, revealed that McSCs are remarkably plastic. This indicates that such cells constantly travel back and forth between compartments of the growing hair follicle during normal hair growth along the maturity axis. McSCs are exposed to various quantities of protein signals that influence maturation within of these compartments.

The research team discovered that McSCs, depending on their location, undergo a transformation between their most basic stem cell state and the following stage of their maturation, the transit-amplifying state.

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 colour 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 greying 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 signalling 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 signalling 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 ageing. These cells remained incapable of regenerating or maturing into pigment-producing melanocytes.

The stuck McSCs, the researchers found, ceased their regenerative behaviour as they were no longer exposed to much WNT signalling 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 greying and loss of hair colour,” 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 coloured,” said Ito, a professor in the Department of Cell Biology at NYU Langone.

It says the team has plans to investigate means of restoring the motility of McSCs or of physically moving them back to their germ compartment, where they can produce pigment.