β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis
β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis
复制标题
毛囊真皮干细胞中β-连环蛋白的激活诱导异位毛发生长和皮肤纤维化
DOI：
10.1093/jmcb/mjy032
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发表时间：
2019
影响因子：
5.5
通讯作者：
Gang Ma
中科院分区：
文献类型：
--
作者：
Yixin Tao;Qingchun Yang;Lei Wang;Jie Zhang;Xuming Zhu;Qianqian Sun;Yunbin Han;Qian Luo;Yushu Wang;Xizhi Guo;Ji Wu;Baojie Li;Xiao Yang;Lin He;Gang Ma
毛囊真皮鞘（Hair follicle dermal sheath， DS）中含有毛囊真皮干细胞（Hair follicle dermal stem cells, hfdsc），可以用来补充毛囊真皮鞘和真皮乳头（dermal papilla， DP）。体外培养的DS细胞可分化为多种细胞系。然而，目前尚不清楚其可塑性是如何在体内调节的。Wnt/β-catenin信号在维持不同谱系的干细胞中起重要作用，是HF发育和再生所必需的。本研究报道了β-catenin在DS中的激活通过重编程HF表皮细胞和DS细胞本身产生异位HF外生长（EF），并赋予DS细胞诱导毛发的能力。原有HFs的表皮稳态被破坏。此外，细胞自主进行性皮肤纤维化在真皮层很突出，那里过多的成纤维细胞主要来源于退行性变性。活化β-catenin纯化的DS细胞的基因表达分析显示，Bmp、Fgf和Notch配体的表达显著增加，Bmp、Fgf或Notch信号抑制剂的使用可减弱EF的形成。总之，我们的研究结果推进了目前对DS细胞高可塑性的认识，并为理解Wnt/β-catenin信号如何控制DS细胞行为提供了新的见解。
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 lineagesin vitro. However, it is unclear how its plasticity is modulatedin 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.