Foxc1 reinforces quiescence in self renewing hair follicle stem cells
Quiescent and aging hair follicle stem cells Stem cells enable normal cell homeostasis, but they also exist in a quiescent state, ready to proliferate and differentiate after tissue damage. Now, two studies reveal features of stem cells in the hair follicle, an epithelial mini organ of the skin that is responsible for hair growth and recycling (see the Perspective by Chuong and Lei) Wang et al. found that the Foxc1 transcription factor is induced in activated hair follicle stem cells, which in turn promote Nfatc1 and BMP signaling, to reinforce quiescence. Matsumura et al. analyzed hair follicle stem cells during aging. They identified type XVII collagen (COL17A1) as key to hair thinning. DNA damage induced depletion of COL17A1 triggered cell differentiation resulting in the shedding of epidermal keratinocytes from the skin surface. These changes then caused hair follicle shrinkage and hair loss. Science, this issue p. 559, p. 613; see also p. 10.1126/science.aad4395 Dynamic expression of a transcription factor sustains the quiescent cellular state in activated hair follicle stem cells during self renewal. [Also see Perspective by Chuong and Lei] 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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