title: Activin A-induced signalling controls hair follicle neogenesis.
abstract: Acquisition of potent human dermal papilla (DP) cells that can induce hair follicle neogenesis is an overarching concern, and various approaches have been tried. In an attempt to solve the problem, we previously introduced the three-dimensional (3D) culture of human DP cells and observed de novo formation of hair follicles when conducting a patch hair reconstitution assay using 3D cultured DP spheres with mouse epidermal cells. In this study, we have subsequently focused our attention on activin A, one of the notably upregulated proteins in DP spheres compared with 2D cultured DP cells. We then adopted a small interfering RNA-mediated gene knock-down approach and hair reconstitution assay to investigate the role of activin A. We observed that human DP spheres with activin A knock-down are severely impaired in hair follicle neogenesis when combined with mouse epidermal cells. In addition, activin receptor 2B (ActvR2B) knock-down mouse epidermal cells showed severe impairment of hair follicle neogenesis when combined with human DP spheres. Moreover, recombinant activin A treatment of mouse epidermal cells increased the expression of downstream genes of the activin pathway. Taken together, our data strongly suggest that activin A-induced signalling plays a critical role in hair follicle neogenesis, which has not been previously reported.
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Seo
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Mi H
authors.initials: MH
authors.lastname: Kwack
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Moon K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Jung C
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Young K
authors.initials: YK
authors.lastname: Sung
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D028341:Activins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: activin A; activin receptor 2B (ActvR2B); dermal papilla; hair follicle neogenesis; three-dimensional (3D) culture