Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18.
Hair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain- and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression.
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, TX 77030, USA.
Erin
E
Leishman
Jeffrey M
JM
Howard
Gloria E
GE
Garcia
Qi
Q
Miao
Amy T
AT
Ku
Joseph D
JD
Dekker
Haley
H
Tucker
Hoang
H
Nguyen
D000818:Animals; D002452:Cell Count; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D057809:HEK293 Cells; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D050761:Cyclin-Dependent Kinase Inhibitor p57; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D012097:Repressor Proteins; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors
Fgf18; Foxp1; Mouse; Skin; Stem cells; hair follicle; p57KIP2