Identifying drug targets for neuropsychiatric and neurodevelopmental disorders via brain transcriptome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe University
• Principal Investigator: NOMURA Jun 神戸大学, 医学研究科, 学内講師 (70406528)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経発達症 / 疾患モデル / 染色体操作 / コピー数多型/CNV / 自閉症 / 統合失調症 / 電気生理 / オルガノイド

Outline of Final Research Achievements

Chromosome 1q21.1 is a region containing approximately 1 Mb and 8 genes, and has been reported to be associated with schizophrenia, attention deficit hyperactivity disorder (ADHD), and autism. In this study, we generated human embryonic stem (ES) cells with a deletion of 1q21.1 (1q21.1del) and a duplication of 1q21.1 (1q21.1dup) as disease models of this chromosomal region and analyzed their phenotypes. dup cells showed a tendency toward anti-neuronal differentiation, i.e., a strong retention of stem cell characteristics. In addition, electrophysiological characteristics of these showed a marked increase in spike and burst frequency in both types of neurons compared to control cells.

Free Research Field

脳神経科学

Academic Significance and Societal Importance of the Research Achievements

1q21.1染色体領域は，統合失調症，ADHD，自閉症等様々な精神疾患，神経発達症との相関が示唆されているにもかかわらず，疾患に至るメカニズムが不明であった．今回，疾患の基盤と考えられる脳内神経細胞および神経幹細胞の表現型を明らかにすべく，（1q21.1欠失および重複）細胞モデルを作製，モデルを用いた疾患表現型解析を実施した．神経幹細胞では1q21.1欠失で易神経分化，1q21.1重複では抗神経分化特性と真逆の表現型を認めた一方，電気生理特性はともに発火頻度が高いという結果が得られた．細胞モデルというシンプルなモデルのメリットを生かし，1q21.1領域が直接関与する疾患表現型を明らかとした．