Japanese researchers report that hair graying and melanoma can arise from the same melanocyte stem cells, which take different paths depending on DNA damage and local signals. Published online October 6, 2025 in Nature Cell Biology, the University of Tokyo-led study outlines a protective differentiation program that promotes graying and how carcinogens can subvert it to favor melanoma.
Melanocyte stem cells (McSCs) generate the pigment cells that color hair and skin. In mammals, they reside in the bulge–sub-bulge region of hair follicles. Over a lifetime, these cells encounter DNA damage from internal and environmental sources that can influence aging and cancer risk.
In mouse experiments using long-term lineage tracing and gene-expression profiling, the team found that DNA double-strand breaks push McSCs into senescence‑coupled differentiation (seno‑differentiation). Driven by the p53–p21 pathway, this response causes the stem cells to mature and be lost, leading to hair graying and removing damaged cells from the tissue.
By contrast, exposure to certain carcinogens, including 7,12‑dimethylbenz(a)anthracene and ultraviolet‑B radiation, can override that safeguard. Even with DNA damage present, McSCs avoid seno‑differentiation, clonally expand, and retain self‑renewal capacity. Signals from KIT ligand in the surrounding niche and epidermis support this shift, fostering a cancer‑prone state that can seed melanoma.
Lead author Yasuaki Mohri and senior author Emi K. Nishimura of The Institute of Medical Science at the University of Tokyo said the same stem cell population can either exhaust or expand depending on the type of stress and microenvironmental cues. The researchers emphasized that graying itself does not prevent cancer; rather, seno‑differentiation is a stress‑triggered defense that clears compromised cells before they become harmful.
The work, published in Nature Cell Biology, connects tissue aging phenotypes with cancer formation by showing how stem cell fates—exhaustion versus expansion—are set under different genotoxic conditions. It also highlights the role of natural "senolysis," or removal of compromised cells, in maintaining tissue health over time.
