“Stuck” stem cells linked with hair graying: Study

A new study shows certain stem cells to 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.

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 online 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.

Reference:

De-differentiation maintains melanocyte
stem cells in a dynamic niche”,Nature,doi 10.1038/s41586-023-05960-6