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Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state

Authors
 Yingzi Liu  ;  Christian F Guerrero-Juarez  ;  Fei Xiao  ;  Nitish Udupi Shettigar  ;  Raul Ramos  ;  Chen-Hsiang Kuan  ;  Yuh-Charn Lin  ;  Luis de Jesus Martinez Lomeli  ;  Jung Min Park  ;  Ji Won Oh  ;  Ruiqi Liu  ;  Sung-Jan Lin  ;  Marco Tartaglia  ;  Ruey-Bing Yang  ;  Zhengquan Yu  ;  Qing Nie  ;  Ji Li  ;  Maksim V Plikus 
Citation
 DEVELOPMENTAL CELL, Vol.57(14) : 1758-1775.e7, 2022-07 
Journal Title
DEVELOPMENTAL CELL
ISSN
 1534-5807 
Issue Date
2022-07
MeSH
Animals ; Calcium-Binding Proteins / metabolism ; Cells, Cultured ; Fibroblasts / metabolism ; Hair ; Hair Follicle* / metabolism ; Hedgehog Proteins* / metabolism ; Humans ; Mice ; SOXF Transcription Factors / metabolism ; Transforming Growth Factor beta / metabolism
Keywords
Hedgehog pathway ; Leptin receptor ; Scube3 ; dermal papilla ; fibroblasts ; hair follicle ; hair growth ; stem cell niche
Abstract
Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche. Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5ahigh states. Transcriptionally, mutant fibroblasts activate regulatory networks for Gli1, Alx3, Ebf1, Hoxc8, Sox18, and Zfp239. These networks jointly upregulate secreted factors for multiple hair morphogenesis and hair-growth-related pathways. Among these is non-conventional TGF-β ligand Scube3. We show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient to induce new hair growth, and pharmacological TGF-β inhibition rescues mutant hair hyper-activation phenotype. Moreover, dermal-papilla-enriched expression of SCUBE3 and its growth-activating effect are partially conserved in human scalp hair follicles. Thus, Hedgehog regulates mesenchymal niche function in the hair follicle via SCUBE3/TGF-β mechanism.
Full Text
https://www.sciencedirect.com/science/article/pii/S1534580722004142
DOI
10.1016/j.devcel.2022.06.005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Oh, Ji Won(오지원) ORCID logo https://orcid.org/0000-0001-5742-5120
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190692
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