Scientists have discovered how DNA damage in stem cells can determine whether hair turns gray or becomes vulnerable tocancer. A new study published on October 6, 2025, inNature Cell Biologyby researchers from The University of Tokyo explains how melanocyte stem cells (McSCs) in hair follicles respond differently to various forms of DNAstress. The work, led by Professor Emi Nishimura and Assistant Professor Yasuaki Mohri, reveals that the same population ofstem cellscan either stop regenerating, leading to graying hair, or expand abnormally, increasing cancer risk. Melanocyte stem cells reside in the bulge-sub-bulge area of hair follicles and serve as the source for pigment-producing melanocytes that give hair its color. The researchers aimed to understand how these stem cells handle DNA damage accumulated over time from internal and environmental sources such as UV exposure or chemical carcinogens, both of which influence tissue aging and cancer development. Using long-term lineage tracing and gene expression profiling in mouse models, the researchers analyzed how McSCs reacted to DNA double-strand breaks and exposure to carcinogens. They induced DNA damage through controlled radiation and chemical exposure, tracking how individual stem cells changed over time. Molecular analyses focused on the activation of stress response pathways, particularly the p53-p21 system, to determine how cells decide between differentiation and renewal. When McSCs experienced double-strand DNA breaks, they entered a process called senescence-coupled differentiation, or seno-differentiation. In this state, the cells permanently matured and exited the stem cell cycle, leading to pigment loss and hair graying. However, when exposed to carcinogens such as 7,12-dimethylbenz(a)anthracene or ultraviolet B rays, this protective mechanism was bypassed. Instead, the damaged cells continued to proliferate with assistance from KIT ligand signals released by nearby tissues. This unchecked renewal drove clonal expansion, setting the stage for potential melanoma formation. According to Nishimura, the results show that stem cells can follow opposing fates-protective aging or malignant growth-depending on the stress type and surrounding tissue signals. These discoveries bridge a vital gap between aging and cancer research, revealing how cellular self-destruction helps maintain tissue health and prevent tumor formation. Reference:Yasuaki Mohri, Jialiang Nie, Hironobu Morinaga, Tomoki Kato, Takahiro Aoto, Takashi Yamanashi, Daisuke Nanba, Hiroyuki Matsumura, Sakura Kirino, Kouji Kobiyama, Ken J. Ishii, Masahiro Hayashi, Tamio Suzuki, Takeshi Namiki, Jun Seita, Emi K. Nishimura. Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma. Nature Cell Biology, 2025; 27 (10): 1647 DOI: 10.1038/s41556-025-01769-9