A Cell Polarity Protein, aPKCλ, Is Essential for Maintaining Hair Follicle Stem Cell Quiescence and Hair Follicle Regeneration

In 2016, a study was conducted on mutant mice to examine the role of a cell polarity protein, aPKCλ, in hair follicle stem cell (HFSC) quiescence and hair follicle regeneration. The mutant mice, which had an epidermal specific deletion of aPKCλ, showed abnormal hair cycling, progressive hair loss, and altered differentiation into the epidermis and sebaceous gland. The study found that the loss of aPKCλ led to a decrease in the expression level of quiescence-inducing factors (Fgf18 and Bmp6), which resulted in the loss of HFSC quiescence. This dysregulation led to an increase in Lrig1-positive cells, causing hyperplasia of the interfollicular epidermis and sebaceous glands, and an increase in Lef1-positive matrix cells, causing a prolonged anagen-like phase. The persistent activation of bulge stem cells led to a gradual depletion of CD34- and integrin a6-positive HFSC reservoirs. Furthermore, hair follicle regeneration after wounding was disturbed in the mutant epidermis, where the expression of Wnt ligands and their downstream targets were severely suppressed. These results suggest that aPKCλ regulates signaling pathways implicated in HFSC quiescence and hair follicle regeneration.