Abstract
Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; however, functional cells with HF inductivity must be expanded in bulk for clinical use. In vitro culture conditions are completely different from the in vivo microenvironment. Although fetal and postnatal dermal cells (DCs) have the potential to induce HFs, they rapidly lose this HF inductivity during culture, accompanied by a drastic change in gene expression. This suggests that epigenetic regulation may be involved. Of the various histone deacetylases (HDACs), Class I HDACs are noteworthy because they are ubiquitously expressed and have the strongest deacetylase activity. This study revealed that DCs from postnatal mice rapidly lose HF inductivity and that this reduction is accompanied by a significant decrease in histone H3 acetylation. However, MS-275, an inhibitor of class I HDACs, preserves HF inductivity in DCs during culture, increasing alkaline phosphatase activity and upregulating HF inductive genes such as BMP4, HEY1, and WIF1. In addition, the inhibition of class I HDACs activates the Wnt signaling pathway, the most well-described molecular pathway in HF development, via increased histone H3 acetylation within the promoter region of the Wnt transcription factor LEF1. Our results suggest that class I HDACs could be a potential target for the neogenesis of HFs.
Highlights
Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; functional cells with HF inductivity must be expanded in bulk for clinical use
We found that inhibition of class I histone deacetylases (HDACs) preserved the HF inductivity of postnatal dermal cells (DCs) during culture via the activation of the Wnt signaling pathway and histone H3 acetylation in the promoter region of LEF1
This evaluation revealed that the expression of the signature genes for HF inductivity, CORIN, BMP4, ALPL, HEY1, and PROM1, all progressively decreased from culture day 1 (CD1) to CD5 (Fig. 1b)
Summary
Induction of new hair follicles (HFs) may be an ultimate treatment goal for alopecia; functional cells with HF inductivity must be expanded in bulk for clinical use. Fetal and postnatal dermal cells (DCs) have the potential to induce HFs, they rapidly lose this HF inductivity during culture, accompanied by a drastic change in gene expression. This suggests that epigenetic regulation may be involved. We found that inhibition of class I HDACs preserved the HF inductivity of postnatal DCs during culture via the activation of the Wnt signaling pathway and histone H3 acetylation in the promoter region of LEF1
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call