Roles of cell cycle inhibition in the genesis of adult neural stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15180
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: The University of Tokyo
• Principal Investigator: Harada Yujin 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (50887825)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 脳 / 神経 / 幹細胞 / 細胞周期 / Notchシグナル

Outline of Final Research Achievements

During embryonic development, neural stem cells actively proliferate and provide many differentiated cells to build the brain. On the other hand, adult neural stem cells contribute to brain homeostasis, learning, and memory by producing newly differentiated cells. We have previously reported that adult neural stem cells in the subventricular zone are derived from slowly dividing neural stem cell populations. In this study, we sought to elucidate the molecular mechanisms by which cell cycle inhibition contributes to the formation of adult neural stem cell lineages. We found that cell cycle inhibition activates Notch-Hey1 signaling, which contributes to the formation and maintenance of adult neural stem cell lineages through a stable expression pattern of Hey1.

Free Research Field

神経発生

Academic Significance and Societal Importance of the Research Achievements

成体哺乳類脳には神経幹細胞が存在し、新たに神経細胞を生み出すことによって脳の恒常性維持や学習・記憶に貢献する。この成体神経幹細胞が発生期幹細胞からどのように作られるかは不明であった。本研究では、成体神経幹細胞が胎生期の分裂を抑制した幹細胞集団に由来し、さらに分裂抑制がNotch-Hey1シグナルによってこれら集団の成体までの長期間の幹細胞維持に貢献することを明らかにした。すなわち本研究は、成体神経幹細胞の形成の始めのステップを分子メカニズムとして解明した研究になると考える。