Abstract
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.
Highlights
Long-term adult stem cells (SCs) are defined by their ability to continuously generate all downstream differentiated cell lineages as well as regenerate themselves throughout the lifetime of an organism (Fuchs and Chen, 2013)
Since Shh-expressing placode cells generate the majority of cells in hair peg, including those still expressing Shh, this intriguing change in cell fate indicates that progenies of Shh-expressing placode cells separate into two different populations: the population still expressing Shh loose the potential to form HFSCs, while the cells with down regulated Shh expression in hair peg can presumably still become HFSCs
Our study elucidates the cascade of events that lead to long-term SC emergence in hair follicles (HFs) during organogenesis (Figure 7)
Summary
Long-term adult stem cells (SCs) are defined by their ability to continuously generate all downstream differentiated cell lineages as well as regenerate themselves throughout the lifetime of an organism (Fuchs and Chen, 2013). It has been postulated that definitive tissue SCs originate from tissue embryonic progenitor cells that acquire the capacity for long-term self-renewal and multipotency at the end of organogenesis (Slack, 2008). Deciphering the process leading to localized SC emergence during normal embryonic development will likely reveal principles that can be used to acquire and maintain the long-term self-renewal and regenerative potentials that are prerequisites for SC-based therapies. The bulge region constitutes the bottom of the permanent portion of a HF It contains two layers of epithelial cells: the CD34- inner layer niche cells and the CD34+ outer layer stem cells. HFs begin to develop in the embryo, the bulge structure is only formed when HFs enter the first postnatal telogen (resting phase); this delineates the end of organogenesis and the emergence of the adult SC niche (Paus et al, 1999; Morris et al, 2004; Tumbar et al, 2004; Blanpain et al, 2004; Zhang et al, 2009; Hsu et al, 2011; Chen et al, 2012)
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