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In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators

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Lien, Wen-Hui [UCL] Polak, Lisa [Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York] Lin, Mingyan [Department of Genetics, Albert Einstein College of Medicine, Bronx, New York] Lay, Kenneth [Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York] Zheng, Deyou [Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York] Fuchs, Elaine [Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York]

Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Here, we unfold genome-wide transcriptional and chromatin landscapes of β-catenin-TCF3/4-TLE circuitry, and genetically dissect their biological roles within the native HFSC niche. We show that during HFSC quiescence, TCF3, TCF4 and TLE (Groucho) bind coordinately and transcriptionally repress Wnt target genes. We also show that β-catenin is dispensable for HFSC viability, and if TCF3/4 levels are sufficiently reduced, it is dispensable for proliferation. However, β-catenin is essential to activate genes that launch hair follicle fate and suppress sebocyte fate determination. TCF3/4 deficiency mimics Wnt-β-catenin-dependent activation of these hair follicle fate targets; TCF3 overexpression parallels their TLE4-dependent suppression. Our studies unveil TCF3/4-TLE histone deacetylases as a repressive rheostat, whose action can be relieved by Wnt-β-catenin signalling. When TCF3/4 and TLE levels are high, HFSCs can maintain stemness, but remain quiescent. When these levels drop or when Wnt-β-catenin levels rise, this balance is shifted and hair regeneration initiates. © 2014 Macmillan Publishers Limited. All rights reserved.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2014
Language Anglais
Journal information "Nature Cell Biology" - Vol. 16, no. 2, p. 179-190 (2014)
Peer reviewed yes
Publisher Nature Publishing Group
e-issn 1476-4679
issn 1465-7392
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
Links
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Bibliographic reference Lien, Wen-Hui ; Polak, Lisa ; Lin, Mingyan ; Lay, Kenneth ; Zheng, Deyou ; et. al. In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. In: Nature Cell Biology, Vol. 16, no. 2, p. 179-190 (2014)
Permanent URL http://hdl.handle.net/2078.1/159703