The role of epigenetic regulator in neural stem cell maintenance and differentiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Jichi Medical University
• Principal Investigator: Tominaga Kaoru 自治医科大学, 医学部, 教授 (20265242)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 神経幹細胞 / エピジェネティクス / ヒストンアセチル化 / 神経発生 / 神経分化 / マウスモデル

Outline of Final Research Achievements

Epigenetic mechanism via chromatin regulation is crucial for many aspects of biological processes including maintenance of stem cells. Histone acetylation is a major epigenetic modification for these processes. Tip60 is one of the histone acetyltransferases (HATs) and is expressed in brain at relatively high levels. To investigate the role of histone acetylation via Tip60 in brain, we have produced the neural stem/progenitor cell specific Tip60 deficient mice. Although Tip60 deficient mice were born in accordance with Mendelian ratio, they died soon after delivery. The Tip60 deficient mice were microcephaly, and this was caused reduced self-renewal ability of their neural stem/progenitor cells and reduced neurogenesis. Analysis of gene expression in Tip60 deficient brain showed reduced expression in a subset of genes relating to neurogenesis. These results suggest that gene regulation controlled by Tip60 has a pivotal role in maintenance and function of neural stem/progenitor cells.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

神経系の構築にはエピジェネティックな調節機構が関与し、その破綻が神経幹細胞の維持や神経発生、高次脳機能に大きな影響を与えると考えられる。近年、精神神経疾患の病態・発症機序の点においてもエピジェネティック因子が注目されている。本研究よりTip60を介したヒストンアセチル化制御は神経幹細胞の維持や神経発生に必須であることが明らかとなり、神経変性疾患や精神神経疾患への関与や病態解明への発展が期待される。