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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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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

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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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