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 α3 in TA cells that signals through an LATS-independent FAK/CDC42/PP1A cascade to control YAP-S397 phosphorylation and nuclear localization. This leads toRhebexpression 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.

中文翻译：

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FAK-YAP-mTOR信号轴调节小鼠干细胞为基础的组织更新。

组织稳态需要从常驻成体干细胞中产生新分化的细胞。该过程的核心是称为分化扩增（TA）细胞的未分化中间体的扩增，但是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未决问题。使用持续增长的小鼠门牙作为基于干细胞的组织更新的模型，我们发现转录辅助因子YAP和TAZ既需要维持TA细胞增殖并抑制分化。具体而言，我们确定了一条涉及TA细胞中整合素α3激活的途径，该途径通过不依赖LATS的FAK / CDC42 / PP1A级联来控制YAP-S397磷酸化和核定位。这导致Rhebexpression并增强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过程中协调干细胞扩增和分化的YAP / TAZ信号传导机制。