毛乳头细胞分泌的FGF7调控毛囊干细胞增殖与分化

doi:10.1016/j.jia.2023.10.012

摘要/Abstract

摘要：

羊绒由绒山羊次级毛囊产生，是纺织业的重要原料之一。根据绒山羊毛囊结构变化，绒山羊毛囊周期可分为生长期、休止期和退行期。绒山羊毛囊周期进入生长期的快慢和生长期维持稳定会直接影响羊绒产量。毛囊干细胞 (Hair follicle stem cell, HFSC) 位于毛囊隆凸区，具有自我更新和分化的特性，也是研究再生医学的干细胞模型之一。毛乳头细胞 (Dermal papilla cell, DPC) 位于毛乳头区域，在毛囊周期转换过程中，DPC发出生长信号作用于HFSC并激活HFSC，使其开始增殖和分化，为毛囊发育提供结构细胞。因此，DPC与HFSC之间的相互作用在毛囊发育和周期转换过程中发挥着重要作用。FGF7是一种外分泌蛋白，参与调控上皮细胞的增殖、分化和迁移。单细胞转录组数据和组织免疫荧光结果显示FGF7定位于DPC，而其受体FGFR2在DPC和HFSC中均表达。酶联免疫吸附试验结果表明，在DPC中添加FGF7过表达腺病毒84 h时，FGF7蛋白在DPC及其培养液中含量最高；利用Tanswell技术将过表达FGF7腺病毒的DPC与HFSC共培养，发现DPC分泌的FGF7促进HFSC的增殖和分化。为进一步研究FGF7对HFSC生物学功能的影响，在HFSC培养基中添加FGF7重组蛋白，结果发现FGF7重组蛋白也能促进HFSC的增殖和分化，与上述结果一致。为了进一步探究FGF7调控HFSC生物学功能的作用机制，利用CUT&Tag技术检测FGF7下游靶基因，结果显示FGF7结合在Wnt信号通路抑制因子GSK3β和多能性相关基因的启动子区。凝胶/电泳迁移率试验（Enzyme-linked immunosorbent assay, EMAS）进一步证明，FGF7与CISH和PRKX基因启动子区相互作用。本研究将绒山羊DPC与HFSC共培养，探究了DPC分泌的FGF7对HFSC生物学功能的调控及其作用机制，阐述了FGF7在绒山羊毛囊再生过程中的作用机理，为外源信号对绒山羊HFSC的调节机制奠定了基础。

Abstract:

Hair follicle stem cell (HFSC), capable of self-renewal and differentiation in hair follicle, represents an emerging stem cell model for regenerative medicine. The interaction between HFSC and dermal papilla cell (DPC) governs hair follicle development. FGF7 functions as a paracrine protein regulating epithelial proliferation, differentiation and migration. The single-cell transcriptome profiling and immunofluorescence analysis demonstrated that FGF7 localizes at DPC, while FGF7 receptor (FGFR2) expresses in both DPC and HFSC. Through co-culture experiments of HFSC and DPC, the results indicated that FGF7 secreted from DPC promotes the proliferation of DPC and HFSC via Wnt signaling pathway and induces HFSC differentiation. Furthermore, CUT&Tag assay revealed genomic colocalization between FGF7 and pluripotency-related genes and GSK3β. Electrophoretic mobility shift assay (EMSA) demonstrated that FGF7 interacts with the promoter region of CISH and PRKX. This research provides valuable insights into the molecular mechanisms underlying the hair cycle. Understanding the interaction between HFSC and DPC, as well as the role of FGF7, may advance regenerative medicine and hair loss treatment.

Key words: FGF7 , dermal papilla cell , hair follicle stem cell , proliferation , differentiation , CUT&Tag assay

Niu Wang, Weidong Zhang, Zhenyu Zhong, Xiongbo Zhou, Xinran Shi, Xin Wang. 毛乳头细胞分泌的FGF7调控毛囊干细胞增殖与分化[J]. Journal of Integrative Agriculture, 2025, 24(9): 3583-3597.

Niu Wang, Weidong Zhang, Zhenyu Zhong, Xiongbo Zhou, Xinran Shi, Xin Wang. FGF7 secreted from dermal papillae cell regulates the proliferation and differentiation of hair follicle stem cell[J]. Journal of Integrative Agriculture, 2025, 24(9): 3583-3597.

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