State Key Laboratory of Chemical Oncogenomics, and the the Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, and Department of Biology, Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, China.
Sci Rep. 2019 Feb 27;9(1):2867. doi: 10.1038/s41598-019-39394-w.
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.
毛囊的发生依赖于皮肤形态发生和再生过程中真皮间充质细胞衍生的信号。多能皮肤来源前体细胞（SKP）在球体培养中表现出长期增殖潜能，已被证明可在小鼠中诱导毛发发生和毛囊再生，这意味着 SKP 在毛囊再生和生物工程中的治疗潜力。然而，SKP 的毛发诱导特性在体外培养扩增过程中逐渐下降，表明负责毛发诱导的基因表达在表观遗传上不稳定。在这项研究中，我们发现 TSA 显著减轻了培养扩增诱导的 SKP 衰老，增加了细胞中碱性磷酸酶（AP）的表达和活性，重要的是恢复了 SKP 的毛发诱导能力。TSA 增加了组蛋白 H3 的乙酰化水平，包括骨形态发生蛋白（BMP）基因启动子区域的 K19/14 位点，这与基因表达和 BMP 信号活性的升高有关，提示 BMP 通路在 TSA 诱导的 SKP 毛发诱导能力恢复中可能起作用。
