Epigenetic memory in neural stem cells establishing individuality

2020 Fiscal Year Final Research Report

• Project Area: Integrative research toward elucidation of generative brain systems for individuality
• Project/Area Number: 16H06527
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Kyushu University
• Principal Investigator: Nakashima Kinichi 九州大学, 医学研究院, 教授 (80302892)
• Co-Investigator(Kenkyū-buntansha): 今村 拓也 広島大学, 統合生命科学研究科(理), 教授 (90390682)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 神経科学 / エピゲノム / 神経幹細胞 / 個性 / ダイレクトリプログラミング / てんかん / 脳梗塞

Outline of Final Research Achievements

It is important to consider the concept of epigenetics for development of the individuality. By focusing on the property of neural stem/progenitor cells (NS/PCs) residing in the adult hippocampus, we identified the mechanism of increased seizure sensitivity in prenatally HDAC inhibitor VPA-exposed adult mice. Furthermore, we found that voluntary exercise can overcome the adverse effects through normalizing VPA-induced transcriptome alterations in NS/PCs.
We also elucidated the mechanism whereby a transcription factor NeuroD1 converts microglia into induced neuronal (iN) cells accompanied by global remodeling of microglial epigenetic signature. Furthermore, iN cells were functionally integrated into brain circuits through synaptic connections with other neurons like endogenous neurons. These findings bring us one step closer to developing therapeutic strategies for nerve injury and disease by reprogramming microglia that accumulate at lesion sites into neurons.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

個性創発にエピジェネティック修飾が関与すると同時に、自発的運動によりけいれん感受性増大という「負の個性」を完全できることを示した。また脳内の非ニューロン細胞をニューロンへと変換しうるとともに、それを利用した新規脳梗塞治療法を開発した。これらは、種々の神経疾患における治療法開発への応用が期待される。