TSA restores hair follicle-inductive capacity of skin-derived precursors

Ling Guo,Xiaoxiao Wang,Meishu Zhu,Ren-He Xu,Yaojiong Wu,Xiaobing Fu,Jifan Yuan,Chuanyue Wu

doi:10.1038/s41598-019-39394-w

Abstract

The genesis of the hair follicle relies on signals derived from mesenchymal cells in the dermis during skin morphogenesis and regeneration. Multipotent skin-derived precursors (SKPs), which exhibit long term proliferation potential when being cultured in spheroids, have been shown to induce hair genesis and hair follicle regeneration in mice, implying a therapeutic potential of SKPs in hair follicle regeneration and bioengineering. However, the hair-inductive property of SKPs declines progressively upon ex vivo culture expansion, suggesting that the expressions of the genes responsible for hair induction are epigenetically unstable. In this study, we found that TSA markedly alleviated culture expansion induced SKP senescence, increased the expression and activity of alkaline phosphatase (AP) in the cells and importantly restored the hair inductive capacity of SKPs. TSA increased the acetylation level of histone H3, including the K19/14 sites in the promoter regions of bone morphogenetic proteins (BMPs) genes, which were associated with elevated gene expression and BMP signaling activity, suggesting a potential attribution of BMP pathway in TSA induced recovery of the hair inductive capacity of SKPs.

Highlights

The genesis of the hair follicle relies on signals derived from mesenchymal cells in the dermis during skin morphogenesis and regeneration[1,2,3]
skin-derived precursors (SKPs) have been shown to migrate into existing dermal papilla (DP) of the hair follicle when being intracutaneously injected and form de novo DPs when implanted in combination with neonatal epidermal cells into excisional wounds[10,11], suggesting their therapeutic potential in hair regeneration
We found that supplementation of Trichostatin A (TSA) into the culture of SKPs could largely restore the hair follicle forming capacity of the cells

Summary

Introduction

The genesis of the hair follicle relies on signals derived from mesenchymal cells in the dermis during skin morphogenesis and regeneration[1,2,3]. When subcutaneously injected in mice the cells were found to incorporate into the DP and induce hair genesis[10], and when transplanted in combination with epidermal stem cells into excisional wounds in mice, SKPs induced de novo hair genesis[11] These results imply a potential application of SKPs in hair follicle regeneration and bioengineering. We found that TSA markedly alleviated culture expansion induced SKP senescence, increased the expression and activity of AP in the cells and importantly restored the hair inductive capacity of SKPs. TSA increased the level of K19/14 acetylation in the promoter regions of bone morphogenetic proteins (BMP) genes, which are associated with elevated gene expression and BMP signaling activity, suggesting a potential attribution of BMP pathway in TSA induced recovery of SKPs’ hair inductive capacity

Methods

Results

Conclusion