The Mesenchymal Niche of the Hair Follicle Induces Regeneration by Releasing Primed Progenitors from Inhibitory Effects of Quiescent Stem Cells

The study explored the role of the dermal papilla (DP) and Sonic hedgehog (Shh) signaling in hair follicle regeneration. It was discovered that the DP initiates hair follicle regeneration by downregulating inhibitory effects on primed progenitors and orchestrates Shh expression, which in turn regulates Wnt signaling activity. Overactivation of Shh in the DP during the anagen phase led to abnormal hair follicle regeneration in subsequent cycles. The study also found that constitutive Shh signaling in the DP during the telogen phase delayed anagen induction and altered stem cell properties, with a reduction in proliferation rate and an increase in Nfatc1 expression, which maintains quiescence. RNA-sequencing revealed significant transcriptional changes in the DP transcriptome due to Shh activation. The study concluded that Shh signaling in the DP upregulates Wnt inhibitors, antagonizing canonical Wnt signaling and delaying anagen initiation. The findings highlight the critical role of the DP and Shh signaling in modulating stem cell activity for hair follicle regeneration. The number of mice used for each genotype was five, with 100 follicles per mouse scored, indicating a moderate sample size for the study.