NFATc1平衡皮肤干细胞的静止和增殖。
NFATc1 balances quiescence and proliferation of skin stem cells.
作者信息
Horsley Valerie, Aliprantis Antonios O, Polak Lisa, Glimcher Laurie H, Fuchs Elaine
机构信息
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
出版信息
Cell. 2008 Jan 25;132(2):299-310. doi: 10.1016/j.cell.2007.11.047.
Quiescent adult stem cells reside in specialized niches where they become activated to proliferate and differentiate during tissue homeostasis and injury. How stem cell quiescence is governed is poorly understood. We report here that NFATc1 is preferentially expressed by hair follicle stem cells in their niche, where its expression is activated by BMP signaling upstream and it acts downstream to transcriptionally repress CDK4 and maintain stem cell quiescence. As stem cells become activated during hair growth, NFATc1 is downregulated, relieving CDK4 repression and activating proliferation. When calcineurin/NFATc1 signaling is suppressed, pharmacologically or via complete or conditional NFATc1 gene ablation, stem cells are activated prematurely, resulting in precocious follicular growth. Our findings may explain why patients receiving cyclosporine A for immunosuppressive therapy display excessive hair growth, and unveil a functional role for calcium-NFATc1-CDK4 circuitry in governing stem cell quiescence.
静止的成体干细胞位于特定的微环境中，在组织稳态和损伤期间，它们会被激活以增殖和分化。目前对干细胞静止状态的调控机制了解甚少。我们在此报告，NFATc1在毛囊干细胞的微环境中优先表达，其表达由上游的BMP信号激活，并且在下游发挥作用，通过转录抑制CDK4来维持干细胞的静止状态。在头发生长过程中，随着干细胞被激活，NFATc1表达下调，解除对CDK4的抑制并激活增殖。当通过药物或完全或条件性NFATc1基因敲除抑制钙调神经磷酸酶/NFATc1信号时，干细胞会过早被激活，导致毛囊过早生长。我们的研究结果可能解释了接受环孢素A进行免疫抑制治疗的患者为何会出现毛发过度生长的现象，并揭示了钙-NFATc1-CDK4信号通路在调控干细胞静止状态中的功能作用。
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