Analysis of DNA methylation changes that determine the differentiation potential of neural stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Keio University
• Principal Investigator: SANOSAKA Tsukasa 慶應義塾大学, 医学部(信濃町), 助教 (40588472)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エピジェネティクス / DNAメチル化 / 神経幹細胞

Outline of Final Research Achievements

Neural stem cells are cells that have self-renewal ability and have potential to differentiate into neurons, astrocytes, and oligodendrocytes that make up the brain and nervous system. However, neural stem cells do not have pluripotency in the early stage of development, and gradually acquire the ability to differentiate into the above-mentioned cell types as development progresses. In this research project, we focused on the epigenetic modification of DNA methylation and analyzed changes in the differentiation potential of neural stem cells. As a result, it was clarified that the methylation state dynamically fluctuates by three steps and the ability to differentiate into each cell type is acquired.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、発生段階に沿った神経幹細胞の性質変化における、DNAメチル化のゲノムワイドな変動が明らかとなった。また、神経幹細胞から各細胞系譜へと運命づけられる際のDNAメチル化の変動も明らかとなり、DNAのメチル化が実際に細胞の分化制御に関与している事が示された。
DNAメチル化は神経系だけでなく、ほとんどすべての細胞種で普遍的にみられる現象であることからも、そのメカニズム解明は他分野への波及効果も大きいと考えられる。