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

Nat Cell Biol. 2014 Feb;16(2):179-90. doi: 10.1038/ncb2903. Epub 2014 Jan 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Mice
  • Mice, Knockout
  • Regeneration
  • Signal Transduction
  • Transcription Factor 4
  • Transcription, Genetic*
  • Wnt Proteins / metabolism*
  • beta Catenin / physiology


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic Helix-Loop-Helix Transcription Factors
  • Tcf3 protein, mouse
  • Tcf4 protein, mouse
  • Transcription Factor 4
  • Wnt Proteins
  • beta Catenin