SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage
The osteoblastic and adipocytic lineages arise from mesenchymal stem cells (MSCs), but few regulators of self-renewal and early cell-fate decisions are known. Here, we show that the Hippo pathway effector YAP1 is a direct target of SOX2 and can compensate for the self-renewal defect caused by SOX2 i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713002465 |
| _version_ | 1828771998460805120 |
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| author | Eunjeong Seo Upal Basu-Roy Preethi H. Gunaratne Cristian Coarfa Dae-Sik Lim Claudio Basilico Alka Mansukhani |
| author_facet | Eunjeong Seo Upal Basu-Roy Preethi H. Gunaratne Cristian Coarfa Dae-Sik Lim Claudio Basilico Alka Mansukhani |
| author_sort | Eunjeong Seo |
| collection | DOAJ |
| description | The osteoblastic and adipocytic lineages arise from mesenchymal stem cells (MSCs), but few regulators of self-renewal and early cell-fate decisions are known. Here, we show that the Hippo pathway effector YAP1 is a direct target of SOX2 and can compensate for the self-renewal defect caused by SOX2 inactivation in osteoprogenitors and MSCs. Osteogenesis is blocked by high SOX2 or YAP1, accelerated by depletion of either one, and the inhibition of osteogenesis by SOX2 requires YAP1. SOX2 favors adipogenesis and induces PPARγ, but adipogenesis can only occur with moderate levels of YAP1. YAP1 induction by SOX2 is restrained in adipogenesis, and both YAP1 overexpression and depletion inhibit the process. YAP1 binds β-catenin and directly induces the Wnt antagonist Dkk1 to dampen pro-osteogenic Wnt signals. We demonstrate a Hippo-independent regulation of YAP1 by SOX2 that cooperatively antagonizes Wnt/β-catenin signals and regulates PPARγ to determine osteogenic or adipocytic fates. |
| first_indexed | 2024-12-11T14:35:52Z |
| format | Article |
| id | doaj.art-a6ac577f0b234f638b9345dd6315517e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T14:35:52Z |
| publishDate | 2013-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a6ac577f0b234f638b9345dd6315517e2022-12-22T01:02:11ZengElsevierCell Reports2211-12472013-06-01362075208710.1016/j.celrep.2013.05.029SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo LineageEunjeong Seo0Upal Basu-Roy1Preethi H. Gunaratne2Cristian Coarfa3Dae-Sik Lim4Claudio Basilico5Alka Mansukhani6National Creative Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 373-1 Guseoung-D, Yuseong-G, Daejeon 305-701, KoreaDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USADepartment of Biology and Biochemistry, University of Houston, Houston, TX 77204, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USANational Creative Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 373-1 Guseoung-D, Yuseong-G, Daejeon 305-701, KoreaDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USADepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USAThe osteoblastic and adipocytic lineages arise from mesenchymal stem cells (MSCs), but few regulators of self-renewal and early cell-fate decisions are known. Here, we show that the Hippo pathway effector YAP1 is a direct target of SOX2 and can compensate for the self-renewal defect caused by SOX2 inactivation in osteoprogenitors and MSCs. Osteogenesis is blocked by high SOX2 or YAP1, accelerated by depletion of either one, and the inhibition of osteogenesis by SOX2 requires YAP1. SOX2 favors adipogenesis and induces PPARγ, but adipogenesis can only occur with moderate levels of YAP1. YAP1 induction by SOX2 is restrained in adipogenesis, and both YAP1 overexpression and depletion inhibit the process. YAP1 binds β-catenin and directly induces the Wnt antagonist Dkk1 to dampen pro-osteogenic Wnt signals. We demonstrate a Hippo-independent regulation of YAP1 by SOX2 that cooperatively antagonizes Wnt/β-catenin signals and regulates PPARγ to determine osteogenic or adipocytic fates.http://www.sciencedirect.com/science/article/pii/S2211124713002465 |
| spellingShingle | Eunjeong Seo Upal Basu-Roy Preethi H. Gunaratne Cristian Coarfa Dae-Sik Lim Claudio Basilico Alka Mansukhani SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage Cell Reports |
| title | SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage |
| title_full | SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage |
| title_fullStr | SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage |
| title_full_unstemmed | SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage |
| title_short | SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage |
| title_sort | sox2 regulates yap1 to maintain stemness and determine cell fate in the osteo adipo lineage |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713002465 |
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