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

Nathan Hawkshaw, Jonathan Hardman, M. Alam, F. Jimenez, Ralf Paus

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Abstract

Background:
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.
Objective:
Recognising the central role of Wnt signalling in hair biology, the differential expression of key agonists, antagonists and target genes of this pathway was delineated during the telogen-to-anagen transformation of human scalp HFs.
Methods:
This was studied by in situ hybridisation in human telogen and early-anagen scalp HF sections.
Results:
Upon 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 (SHG) and the dermal papilla (DP). Conversely, expression of the secreted Wnt-inhibitor, SFRP1 is reduced. Human epithelial HF stem cells up-regulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation.
Conclusion:
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.
Original languageEnglish
JournalBritish Journal of Dermatology
Early online date17 Jul 2019
DOIs
Publication statusPublished - 2019

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