Wang Li, Siegenthaler Julie A, Dowell Robin D, Yi Rui
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Department of Pediatrics, Denver-Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
Science. 2016 Feb 5;351(6273):613-7. doi: 10.1126/science.aad5440.
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.
干细胞静止通过在较长时间内使细胞分裂最小化来维持细胞储备。静止干细胞（SCs）的自我更新需要重新进入细胞周期。在本研究中，我们表明小鼠毛囊干细胞在被激活时会诱导Foxc1转录因子。在激活而非静止的干细胞中删除Foxc1会导致细胞无法重新建立静止状态并允许过早激活。在基因靶向小鼠的干细胞微环境中删除Foxc1会导致旧毛发脱落而不损害静止状态。在自我更新的干细胞中，Foxc1激活Nfatc1和骨形态发生蛋白（BMP）信号传导，这是控制静止的两个关键机制。这些发现揭示了毛囊干细胞在自我更新时用于加强静止的一种动态、细胞内在机制，并表明干细胞具有维持细胞身份的独特能力。
