| Project/Area Number |
26293253
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Fushiki Shinji 京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (80150572)
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| Co-Investigator(Kenkyū-buntansha) |
伊東 恭子 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80243301)
金村 米博 独立行政法人国立病院機構大阪医療センター(臨床研究センター), 再生医療研究室, 室長 (80344175)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 先天異常学 / 神経幹細胞 / 難治性脳形成異常 / 脳オルガノイド / FGFR3 / 胎児医学 / 脳形成障害 |
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| Outline of Final Research Achievements |
We generated novel in vitro cerebral organoids from human-derived neural stem cells (NSCs) in order to clarify the underlying pathomechanisms of brain malformation. Comparative studies on proliferation, cellular migration, and differentiation using control-derived NSCs and thanatophoric dysplasia (TD)-derived NSCs were conducted. Although proliferation potency was similar in undifferentiated conditions, GFAP and phosphorylated STAT1 were significantly increased in TD as compared to control NSCs. In differentiated conditions, TD cells highly produced GFAP-positive radial glial cells rather than Tuj1- and doublecortin-positive immature neurons as compared to control cells, under both 2D cell culture and 3D cerebral organoids. The CAGE analyses provided altered expressions of cellular signalling-related genes and brain development-related genes in TD cells, which might unveil the signalling mechanisms of TD-phenotypes.
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