Adult hair follicles undergo repeated cycling of regression (catagen), resting (telogen), and regeneration (anagen), which is maintained by hair follicle stem cells (HFSCs). The initiation of the regenerative cycle and maintenance of HFSC self-renewal capability is not fully understood. Here, by epithelial deletion of Hes1, a major Notch downstream transcriptional repressor, we found that hair growth is retarded but the hair cycle progresses normally. Remarkably, activation of the secondary hair germ (HG) is delayed and the anagen phase is shortened in Hes1-deficient hair follicles. This developmental delay is not associated with a change in follicular lineages. Importantly, an in vivo repetitive depilation assay indicated that Hes1 is required for HFSC self-renewal and long-term hair regeneration. The underlying mechanism involves Hes1-mediated modulation of Shh responsiveness in anagen, during which Hes1 is specifically upregulated in the lower bulge/HG. Without Hes1, ciliogenesis is affected and Shh signaling is compromised. We reveal a critical function of Hes1 in potentiating Shh signaling in anagen initiation, which allows sufficient signaling strength to expand the HG and replenish HFSCs to maintain the hair cycle.
Date:
2018-05
Relation:
Journal of Investigative Dermatology. 2018 May;138(5):S225.
