Biomaterial Database

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen-anagen transformation. 2020

N J Hawkshaw, and J A Hardman, and M Alam, and F Jimenez, and R Paus

Centre for Dermatology Research, The University of Manchester and NIHR Biomedical Research Centre, Manchester, U.K.

The signals that induce anagen (growth) in 'quiescent' human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen-to-anagen transformation of human scalp HFs. This differential expression was studied by in situ hybridization in human telogen and early-anagen scalp HF sections. On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled-related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation. We provide the first evidence that key changes in Wnt signalling that drive murine anagen induction also occur in human scalp HFs, yet with notable differences. This provides a rational basis for Wnt-targeting therapeutic interventions to manipulate human hair growth disorders. What's already known about this topic? Upregulation of Wnt agonists and downregulation of Wnt antagonists in the secondary hair germ and/or dermal papilla drives hair growth (anagen) induction in mice. Autocrine Wnt signalling in murine epithelial hair follicle stem cells is required to maintain their stem cell function. Reduction of Wnt ligands or increased expression of Wnt antagonists induces dysregulation of the murine hair follicle cycle and causes alopecia. What does this study add? This study demonstrates for the first time that key Wnt pathway regulatory agonists, antagonists and target genes, are expressed in the human telogen-to-early-anagen transformation. On human anagen induction the Wnt ligands WNT3, WNT4 and WNT10B are increased in the regenerating epithelium, whereas the Wnt antagonist, SFRP1 (secreted frizzled-related protein 1), is reduced. Human anagen induction has fundamental differences in the expression of Wnt ligands compared with the murine system. What is the translational message? Regulation of these Wnt ligands permits targeted therapeutic interventions in human hair growth disorders and informs development of new drugs that promote or suppress anagen induction.

UI	MeSH Term	Description	Entries
D006197	Hair	A filament-like structure consisting of a shaft which projects to the surface of the SKIN from a root which is softer than the shaft and lodges in the cavity of a HAIR FOLLICLE. It is found on most surfaces of the body.	Fetal Hair,Hair, Fetal,Lanugo,Fetal Hairs,Hairs,Hairs, Fetal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000505	Alopecia	Absence of hair from areas where it is normally present.	Alopecia, Androgenetic,Baldness,Male Pattern Baldness,Pseudopelade,Alopecia Cicatrisata,Alopecia, Male Pattern,Androgenetic Alopecia,Androgenic Alopecia,Baldness, Male Pattern,Female Pattern Baldness,Hair Loss,Pattern Baldness,Alopecia Cicatrisatas,Alopecia, Androgenic,Alopecias, Androgenic,Androgenic Alopecias,Baldness, Female Pattern,Baldness, Pattern,Hair Losses,Loss, Hair,Losses, Hair,Male Pattern Alopecia
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012535	Scalp	The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).	Scalps
D051153	Wnt Proteins	Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.	Wingless Type Protein,Wnt Factor,Wnt Protein,Wingless Type Proteins,Wnt Factors,Factor, Wnt,Protein, Wingless Type,Protein, Wnt,Type Protein, Wingless
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D060449	Wnt Signaling Pathway	A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, and the vertebrate INT gene. The signaling pathway is initiated by the binding of WNT PROTEINS to cell surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.	Wnt Signaling,Wnt Pathway,Wnt Pathway, Canonical,Wnt beta-Catenin Signaling Pathway,Canonical Wnt Pathway,Canonical Wnt Pathways,Pathway, Canonical Wnt,Pathway, Wnt,Pathway, Wnt Signaling,Signaling Pathway, Wnt,Signaling, Wnt,Wnt Signaling Pathways,Wnt Signalings,Wnt beta Catenin Signaling Pathway
D018859	Hair Follicle	A tube-like invagination of the EPIDERMIS from which the hair shaft develops and into which SEBACEOUS GLANDS open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. (Stedman, 26th ed) Follicles of very long hairs extend into the subcutaneous layer of tissue under the SKIN.	Follicle, Hair,Follicles, Hair,Hair Follicles