Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

Elife. 2015 Dec 14;4:e10567. doi: 10.7554/eLife.10567.


Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.

Keywords: Wnt; developmental biology; hair follicle; mouse; niche; regeneration; self-renewnal; stem cell; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hair Follicle / embryology*
  • Mice
  • Organogenesis*
  • Stem Cells / physiology*
  • Wnt Signaling Pathway*

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.