Age-related neurogenesis decline and onset mechanism of dementia

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15382
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Honda Mizuki 京都大学, 医学研究科, 特定助教 (50828978)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 空間オミクス解析 / 神経幹細胞 / RNA-seq / エピゲノム / ゲノム解析技術

Outline of Final Research Achievements

In this study, our goal is to elucidate the gene expression regulation of neural stem cells (NSCs) associated with aging. To achieve this, we utilize Photo-Isolation Chemistry (PIC), a method we have developed to acquire gene expression information limited to regions of UV irradiation on tissue sections. However, PIC is only compatible with unfixed tissue sections, presenting challenges with staining NSCs, other neural components, and aging markers in unfixed tissue. Therefore, we have improved the PIC technique to enable analysis of formalin-fixed tissue sections. Additionally, we have applied PIC to ATAC-seq and ChIL-seq, establishing techniques to spatially analyze open chromatin and histone modifications, respectively.

Free Research Field

システム生物学

Academic Significance and Societal Importance of the Research Achievements

PICを用いることで、従来法では困難だった複雑な脳切片から特定の領域や細胞の遺伝子発現やその制御情報を抽出することが可能である。また、未固定のみならず、ホルマリン固定した凍結切片にも適用可能である。そのため、神経疾患患者の剖検脳の解析にも応用が可能である。したがって、本技術の臨床検体への活用により、神経系疾患の発症や進行メカニズムの理解が深まり、それに基づく新たな治療法や予防法の開発が期待される。