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An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice.

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机构： [1]Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143, USA [2]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China [3]Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA [4]Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA 94143, USA [5]Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA [6]Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA

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关键词： adult stem cells CDC42 epithelium FAK ITGA3 PP1A TAZ tooth YAP

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 α3 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. Copyright © 2017 Elsevier Inc. All rights reserved.

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出版当年[2017]版：

大类 | 1 区

生物

小类 | 1 区细胞与组织工程 1 区细胞生物学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区细胞与组织工程 1 区细胞生物学

第一作者：

第一作者机构： [1]Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143, USA

通讯作者：

通讯机构： [1]Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143, USA [6]Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA

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