Molecular mechanisms of the fate determination of neural stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04671
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Hitoshi Seiji 滋賀医科大学, 医学部, 教授 (70300895)
• Co-Investigator(Kenkyū-buntansha): 中林 一彦 国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557) ; 福家 聡 滋賀医科大学, 医学部, 助教 (20422660)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 神経幹細胞 / 神経発生 / エピジェネティクス / ヒストン修飾

Outline of Final Research Achievements

In this study, we analyzed the function of Bre1a, one of epigenetics factors, in the maintenance of neural stem cells. First, we established Bre1a knockout ES cells from embryonic day 3.5 blastocysts of Bre1a-null mice and also generated tetracycline-regulated Bre1a overexpressing ES cells. By examining these ES cell lines, we found that Bre1a-mediated histone H2B monoubiquitylation regulated the expression of many genes, which resulted in the alteration of proliferation and differentiation of ES cells. We further generated Bre1a conditional knockout mice and analyzed the phenotypes of Bre1a-null mouse embryos. We found that Bre1a knockout modified the self-renewal and multipotential capabilities of neural stem cells. We have been investigating the molecular mechanisms underlying these changes.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脳の発生において極めて重要な役割を果たす神経幹細胞において、様々なエピゲノム修飾因子が織りなすネットワークを解明し、多様な神経細胞・グリア細胞からなる脳が構築される根本原理の一端を明らかにすることができた。