Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin.
Cell Line
Cell Proliferation
/ genetics
Cells, Cultured
Dermis
/ cytology
Extracellular Vesicles
/ metabolism
Eye Proteins
/ genetics
Fibroblasts
/ cytology
Gene Expression Profiling
/ methods
Gene Expression Regulation
Hair Follicle
/ cytology
Humans
Keratinocytes
/ cytology
Nerve Tissue Proteins
/ genetics
Dermal papilla
Exosomes
Extracellular vesicles
Follicular keratinocytes
Fzd4
Hair follicle
NDP
Norrin
β-Catenin
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
14
03
2019
accepted:
14
05
2019
pubmed:
27
6
2019
medline:
1
7
2020
entrez:
26
6
2019
Statut:
ppublish
Résumé
Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts (DFs) on DPC activation and HF growth. We found that these EVs (st-EVs) enhanced HF growth ex vivo. Comparative transcriptomic analysis on DPCs identified specific activation of the NDP gene, encoding the non-Wnt ligand Norrin. We found that Norrin was secreted by st-EVs-stimulated DPCs activating in a noncell autonomous manner β-catenin pathway in follicular keratinocytes (human HF keratinocyte [HHFK]) and hair growth ex vivo. Although Norrin-specific receptor Frizzled4 was barely detected in HHFK, we found its presence in DF-EVs. Accordingly, DF-EVs provided Frizzled4 to potentiate Norrin effects ex vivo. Our study identifies DF-EVs as efficient activators of DPCs and Norrin as a novel modulatory player in HF physiopathology. Stem Cells 2019;37:1166-1175.
Substances chimiques
Eye Proteins
0
NDP protein, human
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1175Informations de copyright
©AlphaMed Press 2019.
Références
Schmidt-Ullrich R, Paus R. Molecular principles of hair follicle induction and morphogenesis. Bioessays 2005;27:247-261.
Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol 2009;19:R132-R142.
Millar SE. Molecular mechanisms regulating hair follicle development. J Invest Dermatol 2002;118:216-225.
Yang C-C, Cotsarelis G. Review of hair follicle dermal cells. J Dermatol Sci 2010;57:2-11.
Reynolds AJ. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis. Development 1992;115:587-593.
Oh JW, Kloepper J, Langan EA et al. A guide to studying human hair follicle cycling in vivo. J Invest Dermatol 2016;136:34-44.
Panteleyev AA, Jahoda CAB, Christiano AM. Hair follicle predetermination. J Cell Sci 2001;114:3419-3431.
Greco V, Chen T, Rendl M et al. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 2009;4:155-169.
Enshell-Seijffers D, Lindon C, Kashiwagi M et al. β-Catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell 2010;18:633-642.
Plikus MV, Mayer JA, de la Cruz D et al. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature 2008;451:340-344.
St-Jacques B, Dassule HR, Karavanova I et al. Sonic hedgehog signaling is essential for hair development. Curr Biol 1998;8:1058-1069.
Andl T, Reddy ST, Gaddapara T et al. WNT signals are required for the initiation of hair follicle development. Dev Cell 2002;2:643-653.
Festa E, Fretz J, Berry R et al. Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 2011;146:761-771.
Zaborowski MP, Balaj L, Breakefield XO et al. Extracellular vesicles: Composition, biological relevance, and methods of study. Bioscience 2015;65:783-797.
Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013;200:373-383.
Tkach M, Théry C. Communication by extracellular vesicles: Where we are and where we need to go. Cell 2016;164:1226-1232.
O'Loughlin AJ, Mäger I, de Jong OG et al. Functional delivery of lipid-conjugated siRNA by extracellular vesicles. Mol Ther 2017;25:1580-1587.
Zhou L, Wang H, Jing J et al. Regulation of hair follicle development by exosomes derived from dermal papilla cells. Biochem Biophys Res Commun 2018;500:325-332.
Rajendran RL, Gangadaran P, Bak SS et al. Extracellular vesicles derived from MSCs activates dermal papilla cell in vitro and promotes hair follicle conversion from telogen to anagen in mice. Sci Rep 2017;7:15560.
Kwack MH, Seo CH, Gangadaran P et al. Exosomes derived from human dermal papilla cells promote hair growth in cultured human hair follicles and augment the hair-inductive capacity of cultured dermal papilla spheres. Exp Dermatol 2019 [Epub ahead of print].
Topouzi H, Logan NJ, Williams G et al. Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles. Exp Dermatol 2017;26:491-496.
Philpott MP, Sanders D, Westgate GE et al. Human hair growth in vitro: A model for the study of hair follicle biology. J Dermatol Sci 1994;7:S55-S72.
Osada A, Iwabuchi T, Kishimoto J et al. Long-term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction. Tissue Eng 2007;13:975-982.
Kiso M, Hamazaki TS, Itoh M et al. Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro. J Dermatol Sci 2015;79:110-118.
Tomita Y, Akiyama M, Shimizu H. PDGF isoforms induce and maintain anagen phase of murine hair follicles. J Dermatol Sci 2006;43:105-115.
Morgan BA. The dermal papilla: An instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harb Perspect Med 2014;4:a015180.
Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev 2000;14:1181-1185.
Berger W, de Pol D, Warburg M, et al. Mutations in the candidate gene for Norrie disease. Hum Mol Genet 1992;1:461-465.
Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye 2015;29:1-14.
Xu Q, Wang Y, Dabdoub A et al. Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 2004;116:883-895.
Ohyama M, Kobayashi T, Sasaki T et al. Restoration of the intrinsic properties of human dermal papilla in vitro. J Cell Sci 2012;125:4114-4125.
Higgins CA, Chen JC, Cerise JE et al. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. Proc Natl Acad Sci USA 2013;110:19679-19688.
Lai MB, Zhang C, Shi J et al. TSPAN12 is a Norrin co-receptor that amplifies frizzled4 ligand selectivity and signaling. Cell Rep 2017;19:2809-2822.
Seitz R, Hackl S, Seibuchner T et al. Norrin mediates neuroprotective effects on retinal ganglion cells via activation of the Wnt/β-catenin signaling pathway and the induction of neuroprotective growth factors in muller cells. J Neurosci 2010;30:5998-6010.
Zeilbeck LF, Müller BB, Leopold SA et al. Norrin mediates angiogenic properties via the induction of insulin-like growth factor-1. Exp Eye Res 2016;145:317-326.
Yano K, Brown LF, Detmar M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J Clin Invest 2001;107:409-417.
Cheng H, Zhang J, Li J et al. Platelet-rich plasma stimulates angiogenesis in mice which may promote hair growth. Eur J Med Res 2017;22:39.
Gordon KA, Tosti A. Alopecia: Evaluation and treatment. Clin Cosmet Investig Dermatol 2011;4:101-106.
Korta DZ, Christiano AM, Bergfeld W et al. Alopecia areata is a medical disease. J Am Acad Dermatol 2018;78:832-834.