Priming Mobilization of Hair Follicle Stem Cells Triggers Permanent Loss of Regeneration After Alkylating Chemotherapy

The study established a model to understand the permanent loss of hair follicle regeneration following alkylating chemotherapy using human hair follicles treated with busulfan and cyclophosphamide. It was found that quiescent hair follicle stem cells (HFSCs) unexpectedly underwent massive proliferation after busulfan treatment, followed by large-scale apoptosis after cyclophosphamide exposure. This process was mediated by the activation of the PI3K/Akt pathway and cell death driven by the p53/p38 pathway. RNA-seq analysis revealed that HFSCs experienced mitotic catastrophe with G2/M checkpoint activation. The study concluded that the priming mobilization of HFSCs led to their loss of resistance to DNA damage, resulting in a permanent loss of regeneration after chemotherapy.