Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2014 Feb;16(2):179-90. doi: 10.1038/ncb2903. Epub 2014 Jan 26.

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

Author information

  • 11] Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller UniversityNew York New York 10065 USA [2].
  • 2Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller UniversityNew York New York 10065 USA.
  • 3Department of Genetics, Albert Einstein College of MedicineBronx New York 10461 USA.
  • 41] Department of Genetics, Albert Einstein College of MedicineBronx New York 10461 USA [2] Department of Neurology, Albert Einstein College of MedicineBronx New York 10461 USA [3] Department of Neuroscience, Albert Einstein College of MedicineBronx New York 10461 USA.

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.

PMID:
24463605
[PubMed - indexed for MEDLINE]
PMCID:
PMC3984009
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk