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

Wen Hui Lien, Lisa Polak, Mingyan Lin, Kenneth Lay, Deyou Zheng, Elaine Fuchs

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)179-190
Number of pages12
JournalNature Cell Biology
Volume16
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Hair Follicle
Catenins
Stem Cells
Stem Cell Niche
Histone Deacetylases
Genes
Chromatin
Regeneration
Cell Survival
Genome

ASJC Scopus subject areas

  • Cell Biology

Cite this

In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. / Lien, Wen Hui; Polak, Lisa; Lin, Mingyan; Lay, Kenneth; Zheng, Deyou; Fuchs, Elaine.

In: Nature Cell Biology, Vol. 16, No. 2, 02.2014, p. 179-190.

Research output: Contribution to journalArticle

Lien, Wen Hui ; Polak, Lisa ; Lin, Mingyan ; Lay, Kenneth ; Zheng, Deyou ; Fuchs, Elaine. / In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. In: Nature Cell Biology. 2014 ; Vol. 16, No. 2. pp. 179-190.
@article{86a7d59137f141afa7582c2e909f22cc,
title = "In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators",
abstract = "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.",
author = "Lien, {Wen Hui} and Lisa Polak and Mingyan Lin and Kenneth Lay and Deyou Zheng and Elaine Fuchs",
year = "2014",
month = "2",
doi = "10.1038/ncb2903",
language = "English (US)",
volume = "16",
pages = "179--190",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators

AU - Lien, Wen Hui

AU - Polak, Lisa

AU - Lin, Mingyan

AU - Lay, Kenneth

AU - Zheng, Deyou

AU - Fuchs, Elaine

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84895910257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895910257&partnerID=8YFLogxK

U2 - 10.1038/ncb2903

DO - 10.1038/ncb2903

M3 - Article

C2 - 24463605

AN - SCOPUS:84895910257

VL - 16

SP - 179

EP - 190

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 2

ER -