title: Foxc1 reinforces quiescence in self-renewing hair follicle stem cells.
abstract: Stem cell quiescence preserves the cell reservoir by minimizing cell division over extended periods of time. Self-renewal of quiescent stem cells (SCs) requires the reentry into the cell cycle. In this study, we show that murine hair follicle SCs induce the Foxc1 transcription factor when activated. Deleting Foxc1 in activated, but not quiescent, SCs causes failure of the cells to reestablish quiescence and allows premature activation. Deleting Foxc1 in the SC niche of gene-targeted mice leads to loss of the old hair without impairing quiescence. In self-renewing SCs, Foxc1 activates Nfatc1 and bone morphogenetic protein (BMP) signaling, two key mechanisms that govern quiescence. These findings reveal a dynamic, cell-intrinsic mechanism used by hair follicle SCs to reinforce quiescence upon self-renewal and suggest a unique ability of SCs to maintain cell identity.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Denver-Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Siegenthaler
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Dowell
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. yir@colorado.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000505:Alopecia; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000166:cytology* / Q000502:physiology; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C045073:Cre recombinase; D019426:Integrases