Genotoxic insults drive divergent outcomes in melanocyte stem cells (McSCs). Under cytotoxic genotoxin exposure, such as X-ray irradiation, McSC self-renewal is impaired, leading to depletion and hair graying. In homeostasis, McSCs maintain self-renewal and pigment balance. Carcinogenic genotoxins, however, promote KIT signaling and alter arachidonic acid metabolism, giving rise to melanoma founder clones and progression to melanoma.
Throughout life, our cells are constantly exposed to environmental and internal factors that can damage DNA. While such DNA damage is known to contribute to both aging and cancer, the precise connection—particularly how damaged stem cells shape long-term tissue health—has remained elusive.
Melanocyte stem cells (McSCs) are tissue-resident stem cells that serve as the source of mature melanocytes, the pigment-producing cells responsible for hair and skin coloration. In mammals, these stem cells reside in the bulge–sub-bulge region of hair follicles as immature melanoblasts, maintaining pigmentation through cyclical regeneration.
Published in Nature Cell Biology, a study led by Professor Emi Nishimura and Assistant Professor Yasuaki Mohri from The University of Tokyo used long-term in vivo lineage tracing and gene expression profiling in mice to investigate how McSCs respond to different types of DNA damage.
