Elucidation of pathogenesis and development of therapy of lipodystrophy using human iPS cell-derived adipocytes
| Project/Area Number |
25293211
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | National Cardiovascular Center Research Institute (2015-2016)
Kyoto University (2013-2014) |
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Principal Investigator |
Hosoda Kiminori 国立研究開発法人国立循環器病研究センター, 病院, 部長 (40271598)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Kazutoshi 京都大学, iPS細胞研究所, 講師 (80432326)
YAMASHITA Jun 京都大学, iPS細胞研究所, 教授 (50335288)
NAKAO Kazuki 東京大学, 医学研究科, 准教授 (20217657)
Ebihara Ken 自治医科大学, 医学研究科, 准教授 (70362514)
SONE Masakatssu 京都大学, 医学研究科, 特定准教授 (40437207)
SAKURAI Hidetoshi 京都大学, iPS細胞研究所, 講師 (80528745)
FUJIKURA Junji 京都大学, 医学研究科, 助教 (70378743)
NOGUCHI Michio 京都大学, 医学研究科, 特定講師 (00432394)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | seipin / iPS細胞 / 脂肪細胞 / 脂肪萎縮症 / インスリン抵抗性 / レスキュー / 脂肪細胞分化 / 先天性脂肪萎縮症 / 成因解明 |
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| Outline of Final Research Achievements |
Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by marked scarcity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early-onset diabetes. Mutation of the BSCL2/SEIPIN gene causes congenital generalized lipodystrophy. iPS cells were generated from two patients with CGL. Upon adipogenic differentiation, BSCL2-iPS cells exhibited marked reduction of lipid droplet formation concomitant with diffuse cytoplasmic distribution of ADRP, compared with iPS cells from healthy individuals. Forced expression of BSCL2 not only rescued the lipid accumulation defects, but also restored cytoplasmic punctate localization of ADRP in BSCL2-iPS cells. Coimmunoprecipitation indicated SEIPIN interacted with ADRP.
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Report
(5 results)
Research Products
(5 results)
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[Journal Article] Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations2016
Author(s)
1.E. Mori, J. Fujikura, M. Noguchi, K. Nakao, M. Matsubara, M. Sone, D. Taura, T. Kusakabe, K. Ebihara, T. Tanaka, K. Hosoda, K. Takahashi, I. Asaka, N. Inagaki, K. Nakao
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Journal Title
Metablism
Volume: 65
Issue: 4
Pages: 543-556
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production2013
Author(s)
S. H. Chew, Y. Okazaki, H. Nagai, N. Misawa, S. Akatsuka, K. Yamashita, L. Jiang, Y. Yamashita, M. Noguchi, K. Hosoda, Y. Sekido, T. Takahashi, S. Toyokuni
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Journal Title
Carcinogenesis
Volume: 35(1)
Issue: 1
Pages: 164-172
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.2013
Author(s)
M. Noguchi, K. Hosoda, E. Mori, M. Nakane, K. Nakao, D. Taura, Y. Yamamoto, T. Kusakabe, M. Sone, H. Sakurai, J. Fujikura, K. Ebihara, K. Nakao
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Journal Title
Stem Cells and Development
Volume: 22(21)
Issue: 21
Pages: 2895-2905
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 先天性全身性脂肪萎縮症患者からの疾患特異的iPS細胞樹立と解析2015
Author(s)
森栄作, 藤倉純二, 中尾一泰, 野口倫生, 日下部徹, 海老原健, 田中孝之, 浅香勲, 細田公則, 稲垣暢也, 中尾一和
Organizer
第36回日本肥満学会
Place of Presentation
名古屋国際会議場(愛知県名古屋市)
Year and Date
2015-10-02
Related Report
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