β-catenin activation in hair follicle dermal stem cells in duces ectopic hair outgrowth and skin fibrosis

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 

作者机构：Bio-X-Renji Hospital Research CenterRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Bio-X InstitutesShanghai Jiao Tong UniversityShanghai 200240China School of Life Science and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of ProteomicsGenetic Laboratory of Development and DiseasesInstitute of BiotechnologyBeijing 100071China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2019年第11卷第1期

页      面：26-38页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0905[农学-畜牧学] 09[农学] 090501[农学-动物遗传育种与繁殖] 

基　　金：the National Nature Scienee Foundation of China(31671504 and 81421061) the 973 Programs(2013CB967401) the Natural Science Foundation of Shanghai(13ZR1421100) the National Key Technology R&D Program(2012BAI01B09). 

主　　题：Wnt/β-catenin fibrosis hair follicle skin cell differentiation 

摘      要：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 ofβ-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 activatedβ-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.