TY - JOUR
T1 - Stem cells
T2 - Foxc1 reinforces quiescence in self-renewing hair follicle stem cells
AU - Wang, Li
AU - Siegenthaler, Julie A.
AU - Dowell, Robin D.
AU - Yi, Rui
N1 - Funding Information:
We thank members of the Yi laboratory for discussions, P. Muhlrad and T. Cech for critical reading of the manuscript, Y. Han for FACS, K. Diener and B. Gao for Illumina sequencing, J. Tyler for imaging, E. Fuchs (Rockefeller University) for K14-Cre and K14-H2BGFP mice, H. Chang (Stanford University) for help on ATAC-seq, N. Manley (University of Georgia) for Foxn1-Cre mice, and D. Roop and G. Bilousova (University of Colorado, Denver) for Krt6 antibody. This project was partly supported by NIH grant AR066703 and a start-up fund from the University of Colorado Boulder to R.Y. L.W. was supported by an NIH training grant T32GM008759. R.Y. and R.D.D. were coadvisors for L.W. All sequencing data are deposited to GEO with the accession numbers GSE67404 and GSE68288. The authors declare no conflicts of interest.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aad5440
DO - 10.1126/science.aad5440
M3 - Article
C2 - 26912704
AN - SCOPUS:84957574623
VL - 351
SP - 613
EP - 617
JO - Science
JF - Science
SN - 0036-8075
IS - 6273
ER -