Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool

Abstract

SummaryTissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression)1,2. Contrary to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration3. Here we show by intravital microscopy in live mice4–6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbors. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through TGFβ activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviors and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.

Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression

“…Towards the end of Telogen quiescent stem cells from the 2°HG and later from the whole bulge become activated and proliferate to initiate Anagen in order to generate new hair (Blanpain and Fuchs, 2009;Fuchs, 2007). At the end of Anagen, progenitor cells and transit-amplifying cells stop proliferating and undergo apoptosis (Catagen) leading to HF shortening and entrance into the quiescent Telogen phase (Greco et al, 2009;Ito et al, 2004;Mesa et al, 2015;Tumbar et al, 2004).…”

Skin and Its Regenerative Powers: An Alliance between Stem Cells and Their Niche

“…During this time, most of the cycling portion of the hair follicle is lost, with the exception of the upper ORS, which houses cells with HFSC potential and which form a new bulge and HG for the next cycle (Hsu et al, 2011; Mesa et al, 2015). The destructive phase of the hair cycle has served as a convenient means of distinguishing long- and short-term progenitors in the HF.…”

Regeneration Genetics

“…Studies to date have focused on tracking one or two specific cell types in two-dimensional space. For instance, through spatial visualization of both hair follicle cells and adjacent dermal papilla cells, recent live imaging combined with cell ablation found that dermal papilla cells in the mesenchyme are essential to regulate follicular stem cell division during growth and regression phases (75; 99). The finding provides a direct support for the niche function of dermal papilla cells in initiating and sustaining hair regeneration (20).…”