The hair cycle represents a paradigm for studying stem cell quiescence and activation, as well as progenitor cell proliferation, differentiation, and death. Adult hair follicles undergo repeated cycling of regression (catagen), resting (telogen), and growth (anagen), which is maintained by hair follicle stem cells (HFSCs). Adult stem cells maintain tissue homeostasis and regeneration throughout an animal’s lifetime However, the mechanism underlying hair growth initiation and HFSC maintenance is not completely clear.
Dr. Liang‐Tung Yang from the Institute of System Medicine reported hair growth retardation after epithelial deletion of Hes1, a major Notch downstream transcriptional repressor, while the hair cycle progressed normally. Hes1 is specifically upregulated in the lower bulge/ hair germ (HG) during anagen initiation. Accordingly, loss of Hes1 resulted in delayed activation of the secondary HG and shortened anagen phase. This developmental delay caused reduced hair shaft length but not identity changes in follicular lineages. Remarkably, Hes1 ablation resulted in impaired hair regeneration upon repetitive depilation. Microarray gene profiling on HFSCs indicated that Hes1 modulated Shh responsiveness in anagen initiation. Using primary keratinocyte cultures, Dr. Yang demonstrated that Hes1 deletion negatively influenced ciliogenesis and Smoothened ciliary accumulation upon Shh treatment. Furthermore, transient application of Smoothened agonist during repetitive depilation can rescue anagen initiation and HFSC self-renewal in Hes1-deficient hair follicles. These findings suggested that Hes1 reinforced the Shh signaling during telogen‐anagen transition to maintain hair cycle homeostasis.
Citation: Suen, WJ; Li, ST; Yang, L. Hes1 regulates anagen initiation and hair follicle regeneration through modulation of hedgehog signaling. Stem Cells. 2020 Feb;38(2):301-314.