Gasdermin A3-Mediated Cell Death Causes Niche Collapse and Precocious Activation of Hair Follicle Stem Cells

The study investigated the effects of Gasdermin A3 (Gsdma3) overexpression on hair follicle stem cells (HFSCs) in mice, revealing that Gsdma3-mediated cell death disrupted the HFSC niche and caused premature activation of HFSCs. This led to abnormal hair cycle progression and hair follicle degeneration, mimicking scarring alopecia in humans. The research demonstrated that the hair loss was not due to immune-mediated mechanisms, as topical immunosuppressants did not prevent cell death. Instead, Gsdma3-induced cell necrosis caused hair shedding and immediate re-entry into the anagen phase, bypassing the telogen phase, highlighting the role of Gsdma3 in maintaining HFSC niche integrity.