@article{6a707795c40b43ee9aea472f296602c9,
title = "Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state",
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.",
keywords = "dermal papilla, fibroblasts, hair follicle, hair growth, Hedgehog pathway, Leptin receptor, Scube3, stem cell niche",
author = "Yingzi Liu and Guerrero-Juarez, {Christian F.} and Fei Xiao and Shettigar, {Nitish Udupi} and Raul Ramos and Kuan, {Chen Hsiang} and Lin, {Yuh Charn} and {de Jesus Martinez Lomeli}, Luis and Park, {Jung Min} and Oh, {Ji Won} and Ruiqi Liu and Lin, {Sung Jan} and Marco Tartaglia and Yang, {Ruey Bing} and Zhengquan Yu and Qing Nie and Ji Li and Plikus, {Maksim V.}",
note = "Funding Information: M.V.P. is supported by LEO Foundation grants LF-AW-RAM-19-400008 and LF-OC-20-000611 , Chan Zuckerberg Initiative grant AN-0000000062 , W.M. Keck Foundation grant WMKF-5634988 , NSF grant DMS1951144 , and NIH grants U01-AR073159 , R01-AR079470 , R01-AR079150 , R21-AR078939 , and P30-AR075047 . Additional support comes from the NSF grant DMS1763272 and Simons Foundation grant ( 594598 , Q.N.). J.L. is supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China ( 91749114 ) and National Natural Science Foundation of China ( 81773351 ); Y.L. by the National Natural Science Foundation of China (82073467) ; R.-B.Y. by Ministry of Science and Technology of Taiwan ( MOST 109-2320-B-001-012-MY3 ); Y.-C.L. by MOST 110-2326-B-001-004-MY3 ; C.F.G.-J. by UC Irvine Chancellor{\textquoteright}s ADVANCE Postdoctoral Fellowship Program , NSF-Simons Postdoctoral Fellowship ( DMS1763272 , to Q.N.), Simons Foundation grant ( 594598 , to Q.N.), and by a generous gift from the HHMI Hanna H. Gray Postdoctoral Fellowship Program ; L.J.M.L. by UC-MEXUS CONACYT and Fullbright-Garcia Robles doctoral fellowships. The authors would like to thank Shenghan Chen and Junyu Nan for their help with mouse husbandry and genotyping. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = jul,
day = "25",
doi = "10.1016/j.devcel.2022.06.005",
language = "English",
volume = "57",
pages = "1758--1775.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "14",
}