Modulation of lipid homeostasis in maintenance and directed differentiation of mesenchymal stem cells
Project/Area Number |
16H05529
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dental engineering/Regenerative dentistry
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
福本 敏 東北大学, 歯学研究科, 教授 (30264253)
齋藤 正寛 東北大学, 歯学研究科, 教授 (40215562)
竹田 浩之 愛媛大学, プロテオサイエンスセンター, 准教授 (40609393)
福島 秀文 東北大学, 歯学研究科, 准教授 (70412624)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
|
Keywords | タンパク質分解 / 脂質代謝 / Lipin1 / beta-TRCP / 間葉系幹細胞 / 歯髄幹細胞 / SCF/beta-TRCP / 蛋白質分解 / ユビキチン-プロテアソーム系 |
Outline of Final Research Achievements |
Manipulating lipid biosynthesis in stem cells could be a potential approach for highly efficient directed differentiation of mesenchymal stem cells. In this study, we identified the molecular mechanisms of the proteasome-dependent degradation of Lipin1 that plays critical roles in lipid homeostasis. Our finding will provide insights into the development of novel strategies for the directed differentiation of mesenchymal stem cells through Lipin1 protein stability control.
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Academic Significance and Societal Importance of the Research Achievements |
再生医療研究において間葉系幹細胞の応用が進められているが、幹細胞代謝研究領域での脂質代謝調節に焦点を当てた研究は少ない。薬理学的および遺伝学的アプローチにより脂質合成制御が幹細胞で可能となれば、効率的な細胞分化誘導のほか移植後細胞の脂肪細胞分化転換抑制にも応用可能となることから、本研究で得られた知見は高効率かつ安定的な幹細胞分化誘導法開発の基礎となると期待される。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD42017
Author(s)
Dai X, Gan W, Li X, Wang S, Zhang W, Huang L, Liu S, Zhong Q, Guo J, Zhang J, Chen T, Shimizu K, Beca F, Blattner M, Vasudevan D, Buckley DL, Qi J, Buser L, Liu P, Inuzuka H, Beck AH, Wang L, Wild PJ, Garraway LA, Rubin MA, Barbieri CE, Wong KK, Muthuswamy SK, Huang J, Chen Y, Bradner JE, Wei W
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Journal Title
Nature Medicine
Volume: 23
Issue: 9
Pages: 1063-1071
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] FBW7 loss promotes chromosomal instability and tumorigenesis via Cyclin E1/CDK2-mediated phosphorylation of CENP-A2017
Author(s)
Takada M, Zhang W, Suzuki A, Kuroda T, Yu Z, Inuzuka H, Gao D, Wan L, Zhuang M, Hu L, Zhai B, Fry C, Bloom K, Li G, Karpen G, Wei W, Zhang Q
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Journal Title
Cancer Research
Volume: 77
Pages: 4881-4893
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] G1 cyclins link proliferation, pluripotency and differentiation of embryonic stem cells2017
Author(s)
Lijun Liu, Wojciech Michowski, Hiroyuki Inuzuka, Kouhei Shimizu, Naoe Taira Nihira, Joel M. Chick, Na Li, Yan Geng, Alice Y. Meng, Alban Ordureau, Aleksandra Kolodziejczyk, Keith L. Ligon, Roderick T. Bronson, Kornelia Polyak, J. Wade Harper, Steven P. Gygi, Wenyi Wei, Piotr Sicinski
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Journal Title
Nature Cell Biology
Volume: 19
Issue: 3
Pages: 177-188
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function2017
Author(s)
Wan L, Chen M, Cao J, Dai X, Yin Q, Zhang J, Song SJ, Lu Y, Liu J, Inuzuka H, Katon JM, Berry K, Fung J, Ng C, Liu P, Song MS, Xue L, Bronson RT, Kirschner MW, Cui R, Pandolfi PP, Wei W
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Journal Title
Cancer Discovery
Volume: 7
Issue: 4
Pages: 424-441
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017
Author(s)
Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
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Journal Title
Sci Signal. doi: 10.1126/scisignal.aah4117.
Volume: 10
Issue: 460
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN couplex localization and promotes renal cancer progression2016
Author(s)
Nagashima, K., Fukushima, H., Shimizu, K., Hidaka, M., Hasumi, H., Ikebe, T., Fukumoto, S., Okabe, K., Inuzuka, H.
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Journal Title
Oncotarget
Volume: 8
Issue: 6
Pages: 9947-9960
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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