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

Long-term adult stem cells sustain tissue homeostasis and regeneration throughout the lifetime of an organism. They are thought to originate from embryonic progenitors that acquired long-term self-renewal ability and multipotency at the end of organogenesis. We aim to mechanistically understand the embryonic origin of localized hair follicle stem cells. Here we discover embryonic progenitor cells occupying upper hair peg location; expressing a stem cell marker Nfatc1, contribute to long-term hair follicle stem cells, while the ones locating in the lower hair peg, expressing Shh, acquire differentiated cell fate. To understand the underlying mechanism leading to niche-induced HFSC specification, we profiled the expression of mRNA isolated from purified hair peg cells expressing Shh or Nfatc1. Based on DAVID functional gene annotation analysis, among genes that were expressed 2 fold more in Shh+ cells than in Nfatc1+ cells, we found that genes of the Wnt signaling pathway were enriched prominently. Base on these result and further genetic study, we suggest when hair placode develops to hair peg, a localized Wnt/β-catenin signal free zone emerges. Embryonic progenitors residing in this region gain expression of stem cell markers compared to their precursors and become definitive long-term hair follicle stem cells. Overall design: Shh or Nfatc1 expressing cells at hair peg stage were labelled by genetic tools. Then mRNA isolated from purified hair peg cells expressing Shh or Nfatc1 were profiled.