Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy

The study explored how hair follicles (HFs) responded to genotoxicity-induced injury from chemotherapy and radiotherapy, which often caused hair loss in cancer treatment. It was found that HFs mobilized ectopic progenitors from transit-amplifying cell (TAC) compartments for regeneration, depending on the severity of damage. After low-dose ionizing radiation (IR), keratin 5+ basal hair bulb progenitors were activated to regenerate hair follicles, while high-dose IR led surviving outer root sheath cells to adopt a stem cell-like state for regeneration. The study also showed that IR-induced hair loss was linked to suppressed WNT signaling in a p53-dependent manner. Enhancing WNT signaling reduced the suppressive effects of p53, promoting progenitor proliferation and preventing hair loss. The findings suggested that targeting TAC-derived progenitor cells for hair follicle repair could be a potential strategy to prevent hair loss from chemotherapy and radiotherapy.