Disruption of Smad4 in Mouse Epidermis Leads to Depletion of Follicle Stem Cells

In a study from 2009, researchers found that disrupting Smad4, a key component of TGF-beta signaling, in the epidermis of young mice led to the overactivation of follicle stem cells (SCs) in the hair follicle bulge. This overactivation caused an increase in the proliferation of these cells, resulting in hyperplasia of the interfollicular epidermis, hair follicles, and sebaceous glands. However, this increased activity eventually depleted the stem cell niche, as evidenced by the loss of bromodeoxyuridine (BrdU) label-retaining cells, and a decrease in keratin 15 (K15) and CD34 expression. Additionally, the colony-forming efficiency of keratinocytes from the Smad4 mutant mice was significantly reduced. The depletion of follicle SCs was associated with increased nuclear localization of beta-catenin and higher expression of c-Myc. The study concluded that Smad4 is crucial for the maintenance of follicle stem cells.