Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability. Epidermal homeostasis of pre-existing HFs is disrupted. Additionally, cell-autonomous progressive skin fibrosis is prominent in dermis, where the excessive fibroblasts largely originate from DS. Gene expression analysis of purified DS cells with activated β-catenin revealed significantly increased expression of Bmp, Fgf, and Notch ligands and administration of Bmp, Fgf, or Notch signaling inhibitor attenuates EF formation. In summary, our findings advance the current knowledge of high plasticity of DS cells and provide an insight into understanding how Wnt/β-catenin signaling controls DS cell behaviors.

中文翻译：

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毛囊真皮干细胞中的β-catenin活化可诱导异位毛发生长和皮肤纤维化。

毛囊真皮鞘（DS）包含毛囊真皮干细胞（hfDSC），可以募集这些干细胞来补充DS和真皮乳头（DP）。培养的DS细胞可以在体外分化为各种细胞系。然而，尚不清楚其可塑性在体内如何调节。Wnt /β-catenin信号传导在维持各种谱系的干细胞中起重要作用，并且是HF发育和再生所必需的。在这里，我们报道了通过重新编程HF表皮细胞和DS细胞本身，DS中β-catenin的活化产生异位HF增生（EF），并使DS细胞具有毛发诱导能力。预先存在的HF的表皮稳态被破坏。另外，细胞自治的进行性皮肤纤维化在真皮中很明显，真皮中过量的成纤维细胞主要来自DS。用活化的β-catenin纯化的DS细胞的基因表达分析表明，Bmp，Fgf和Notch配体的表达显着增加，并且施用Bmp，Fgf或Notch信号抑制剂抑制了EF的形成。总之，