Epidermal stem cells in the isthmus/infundibulum influence hair shaft differentiation: evidence from targeted DLX3 deletion

Distinct stem cell populations are present in the skin that comprises the epidermis and the pilosebaceous unit (hair follicle and sebaceous gland) (Clayton et al., 2007; Mascre et al., 2012). Recent studies have highlighted the strong heterogeneity and compartmentalization of stem cell niches in the skin (Jaks et al., 2010; Page et al., 2013). During telogen (resting phase), hair follicle stem cells are located in the lower part of the hair follicle, in the bulge and hair germ areas, and express markers such as Lgr5, K15 and CD34 (Trempus et al., 2007; Jaks et al., 2010). Upon reentry into anagen (growing phase), components of the new hair are derived from these hair follicle stem cells. Even though they do not contribute to the homeostasis of the epidermis, these cells do participate in regeneration in the context of wound healing (Ito et al., 2005; Levy et al., 2005; Jaks et al., 2008). Recently, epidermal stem cells were identified in the upper part of the hair follicle: in the isthmus that is located near the attachment of the sebaceous gland to the follicle, and in the infundibulum area, which spans the isthmus and the epidermis. These cells express specific markers such as Lrig1 and MST24, and contribute to the formation of the sebaceous gland and to epidermal differentiation in response to injury (Jensen et al., 2009; Page et al., 2013). During anagen, the cells from the isthmus/infundibulum area do not contribute to the formation of the new hair. However, here we show that the deletion of the transcription factor DLX3 in the epidermis and isthmus/infundibulum area, but not in the bulge region, leads to altered hair shaft differentiation without affecting hair growth.