Microenvironmental regulation of neural stem cells and age-related changes by lysosomes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03260
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kyoto University
• Principal Investigator: Kobayashi Taeko 京都大学, 生命科学研究科, 准教授 (40402804)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 成体神経幹細胞 / 休眠 / エクソソーム / リソソーム

Outline of Final Research Achievements

Neural stem cells in the adult brain are mainly in a quiescent state in which they have stopped proliferating and differentiating. We have demonstrated that lysosomes regulate neural stem cell quiescence. We have identified two new regulatory mechanisms in this research project. First, we focused on controlling the stem cell niche, the unique microenvironment for stem cells and analyzed the exosomes of extracellular secretory vesicles. As a result, we revealed translational repression by secreting exosomes with ribosomes in quiescent neural stem cells. Second, we have also developed a new monitoring probe to quantify the proteolytic activity of lysosomes in brain neural stem cells. As a result, we found that lysosomal proteolytic activity is dynamically altered in neural stem cells during brain maturation, brain aging, and brain disease using Alzheimer's model mice. Based on these research results, two original papers were published.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

大人の脳内に存在する神経幹細胞は、ほとんどが増殖や分化を停止した「休眠状態」で維持される。休眠は一生涯に渡って脳内に幹細胞を維持するための必須のメカニズムであるが、加齢に伴って活性化されにくくなるため、脳内での休眠制御の分子機構の解明は、学術的にも非常に重要な課題である。我々は本研究課題によって、２つの新たな神経幹細胞の制御機構を明らかにした。一つは細胞外分泌小胞のエクソソームによる制御であり、もう一つは加齢や疾患に伴う脳内神経幹細胞でのリソソームの機能変化についてである。これらの成果は、神経幹細胞を利用した脳疾患の予防や治療法の開発につながる基礎研究であり、社会的な意義も非常に高い。