2023 Fiscal Year Final Research Report
Unraveling mechanism of pathogenesis in CHAREGE syndrome using iPSC-derived brain organoid
| Project/Area Number |
19H03623
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Keio University |
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Principal Investigator |
KOHYAMA JUN 慶應義塾大学, 医学部(信濃町), 准教授 (30437511)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | CHARGE症候群 / 脳オルガノイド |
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| Outline of Final Research Achievements |
Using iPS cells derived from CHARGE syndrome patients, the research involved brain organoid models to investigate the epigenomic regulatory mechanisms of CHD7's target genes. Methods included histological examination and single-cell level RNA-Seq analyses to explore the target genes and epigenomic states influenced by CHD7. The study found that CHD7 binds with tissue-specific pioneer factors to regulate enhancer activation and identified abnormalities in glial cell maturation. Additionally, a novel factor, Factor X, was discovered to interact with CHD7, forming droplets in the nucleus, particularly in neural progenitor cells, concentrating transcriptional activators and positively regulating CHD7 activity. Inhibition of this droplet formation in Factor X resulted in phenotypes similar to those of CHARGE syndrome patients' iPS cells, suggesting new mechanisms in CHD7 function.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
CHD7遺伝子と関連因子の機能解明により、早期診断や適切な治療法の開発が進むことで、患者の生活の質向上や医療費削減が期待される。また、遺伝的リスクを抱える家族への正確な情報提供や、エピゲノム制御と転写調節の新たな知見の提供を通じて、他の神経発生障害の理解や治療法開発にも寄与する可能性がある。これにより、CHARGE症候群患者やその家族が病気を理解し、対処するための支援が強化され、社会全体の理解が深まることが期待される。
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