Research into Blau syndrome using disease-specific iPS cells
| Project/Area Number |
17K10243
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWASAKI Yuri 京都大学, iPS細胞研究所, 特定研究員 (70507079)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ブラウ症候群 / NOD2 / iPS細胞 / IFN-γ / 自己炎症性疾患 / RNS-seq / RNA-seq / NF-κB / 遺伝学 |
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| Outline of Final Research Achievements |
In order to elucidate the pathophysiology of Blau syndrome caused by NOD2 gene mutation, we conducted a study using disease-specific iPS cells established from patient. This iPS cells were differentiated into macrophages (iPS-MPs) by making full use of their properties, and used as samples of RNA sequencing. As a result, RNA sequencing analysis revealed distinct transcriptional profiles of mutant iPS-MPs. Interestingly, we noticed that inflammatory pathway were already upregulated in mutant iPS-MPs, even in the unstimulated state. In addition, to elucidate the kinetics of the mutant NOD2 protein, a system was constructed to overexpress the mutant NOD2 protein with 3×FLAG-tag. By labeling 3×FLAG-tag, intracellular localization of the mutant NOD2 protein was able to be visualized.
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| Academic Significance and Societal Importance of the Research Achievements |
ブラウ症候群の患者から樹立した疾患特異的iPS細胞と、ブラウ症候群の患者から得られた血液細胞を元にしたRNAシーケンスの解析を行った。どちらの細胞からも同様に「ブラウ症候群の遺伝子変異があると、平常時でも炎症反応が活性化状態にあることが示唆される」という結果を得ることができた。これは、ブラウ症候群の研究に疾患特異的iPS細胞を用いることの有用性を支持するものである。難病に指定され、治療法も確立されていないブラウ症候群にとって、患者の貴重な血液を使用することなく、疾患特異的iPS細胞を用いて研究を推進できることは、病態の解明や治療法開発を発展させるのに意義のあることである。
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Report
(4 results)
Research Products
(2 results)
