High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence

Cell Rep. 2014 Feb 13;6(3):499-513. doi: 10.1016/j.celrep.2013.12.039. Epub 2014 Jan 23.


Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying matrix cells. EPs can revert to SCs upon injury, but whether this dedifferentiation occurs in normal HF homeostasis (hair cycle) and the mechanisms regulating both differentiation and dedifferentiation are unclear. Here, we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression induces hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome toward a cell state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and dedifferentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle* / drug effects
  • Cell Differentiation* / drug effects
  • Cell Proliferation / drug effects
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Down-Regulation / drug effects
  • Gene Expression Profiling
  • Hair Follicle / cytology*
  • Hair Follicle / drug effects
  • Hair Follicle / growth & development
  • Homeostasis / drug effects
  • Homeostasis / genetics
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Tetracycline / pharmacology
  • Time Factors


  • Core Binding Factor Alpha 2 Subunit
  • Runx1 protein, mouse
  • Tetracycline

Associated data

  • GEO/GSE53077