Elucidation of the mechanism of HMGA2-induced transition of neural stem cells from expansion to neurogenic phase

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14622
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kishi Yusuke 東京大学, 大学院薬学系研究科(薬学部), 講師 (00645236)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経幹細胞 / クロマチン / Hmga2

Outline of Final Research Achievements

Most of the neurons, the most important cell types in the brain, are produced from neural stem cells during development. In the early stages of development, neural stem cells increase their number by self-renewal, but at a certain point, they begin to produce neurons. The timing of this fate change should be strictly regulated because it determines the number of neurons that are subsequently produced. However, the regulatory mechanism has been unknown. In this study, we found that the upregulation of Hmga2, a chromatin-regulating factor, during the transition from expansion to neurogenic phases regulates the gene expression pattern of neural stem cells and promotes fate switching.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

神経幹細胞の増殖期からニューロン分化期への運命転換の異常は、成体脳のニューロンやその他の細胞の数の異常につながる。実際に、この運命転換の異常が自閉症などの神経発達障害の原因の一つであると考えられている。
本研究ではこの運命転換のメカニズムとしてHmga2による制御が重要であることを明らかにした。そのため、本研究をもとに神経幹細胞の運命転換のメカニズム、ひいてはヒトの神経発達障害の理解につながると期待される。