FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

Here, the authors suggest that hair follicle stem cells (HFSCs) have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. They examine whether parsimonious stem cells use is essential to conserve long-term tissue-regenerating potential during normal homeostasis by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1).  FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. Hair follicle stem cells lacking the protein FOXC1 can only retain one old bulge in their hair follicles, while normal stem cells can keep up to four. In vitro cell adhesion assay they show that FACS-purified WT and Foxc1-KO HFSCs attach very well to LN-511 with about 6 times higher well area coverage compared to collagen I, fibronectin or Matrigel-coated plates.