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首页> 外文期刊>Cell stem cell >An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice
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An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice

机译：FAK-YAP-MTOR信号轴调节小鼠中基于干细胞的组织更新

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摘要

Tissue homeostasis requires the production of newly differentiated cells from resident adult stem cells. Central to this process is the expansion of undifferentiated intermediates known as transit-amplifying (TA) cells, but how stem cells are triggered to enter this proliferative TA state remains an important open question. Using the continuously growing mouse incisor as a model of stem cell-based tissue renewal, we found that the transcriptional cofactors YAP and TAZ are required both to maintain TA cell proliferation and to inhibit differentiation. Specifically, we identified a pathway involving activation of integrin alpha 3 in TA cells that signals through an LATS-independent FAK/CDC42/PP1A cascade to control YAP-S397 phosphorylation and nuclear localization. This leads to Rheb expression and potentiates mTOR signaling to drive the proliferation of TA cells. These findings thus reveal a YAP/TAZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal.
机译：组织稳态需要从驻留的成人干细胞产生新分化的细胞。该过程的核心是未分化的中间体的扩展，称为过度扩增（TA）细胞，但如何触发干细胞进入这种增殖性TA状态仍然是一个重要的开放问题。使用连续生长的小鼠切入作为基于干细胞的组织更新的模型，我们发现转录辅因子YAP和TAZ都需要维持TA细胞增殖并抑制分化。具体地，我们鉴定了一种涉及通过LAT无关的FAK / CDC42 / PP1A级联信号的TA细胞中整合蛋白α3激活的途径，以控制YAP-S397磷酸化和核定位。这导致RHEB表达和增强MTOR信号传导，以驱动TA细胞的增殖。这些发现因此揭示了在器官更新期间协调干细胞扩张和分化的YAP / TAZ信号机制。

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  • 来源
    《Cell stem cell》 |2017年第1期|共22页
  • 作者

    Hu Jimmy Kuang-Hsien; Du Wei; Shelton Samuel J.; Oldham Michael C.; DiPersio C. Michael; Klein Ophir D.;

  • 作者单位

    Univ Calif San Francisco Dept Orofacial Sci San Francisco CA 94143 USA;

    Univ Calif San Francisco Dept Orofacial Sci San Francisco CA 94143 USA;

    Univ Calif San Francisco Dept Neurol Surg San Francisco CA 94143 USA;

    Univ Calif San Francisco Dept Neurol Surg San Francisco CA 94143 USA;

    Albany Med Coll Ctr Cell Biol &

    Canc Res Albany NY 12208 USA;

    Univ Calif San Francisco Dept Orofacial Sci San Francisco CA 94143 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
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