Epigenetic mechanisms regulating developmental stage-dependent change in cortical neural stem cell property

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kyushu University
• Principal Investigator: Katada Sayako 九州大学, 医学研究院, 助教 (00615685)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 神経発生 / 幹細胞分化 / エピジェネティクス

Outline of Final Research Achievements

During the development of the mammalian cerebral cortex, first emerged neural stem cells have high potency of self-renew, then differentiated into neurons in mid gestation, and then astrocytes in late gestational stage. We have previously reported that DNA demethylation near astrocytic genes is important for acquisition of astrocyte differentiation. Not only that we found several of important transcription factors for neurogenesis acquire DNA methylation at their proximal regions in late gestation. To investigate molecular mechanism of this developmental progression-dependent gain of DNA methylation, we search factors that could bind to these regions and found transcriptional repressor Trim28 as a candidate by ChIP-Atlas. We confirmed that knock down of Trim 28 increased pro-neuronal gene Neurog1 expression and neuronal differentiation. Therefore, we note Trim28 as important epigenetic factor for neural stem cell fate regulation.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

これまで、神経幹細胞のエピジェネティクス制御に関して、ニューロン分化を制御するDNAメチル化修飾は報告がない。着目する発生進行依存的なDNAメチル化領域は、遺伝子発現を制御する重要なエンハンサー領域である可能性が高く、これら領域のエピゲノム制御を担う分子を解明することが出来れば、神経幹細胞分化における新規のエピジェネティクス制御機構の提示のみならず、これを操作することでin vitro培養系においても、長期に高いニューロン分化能力を備えた神経幹細胞の維持など、応用面における貢献も期待が高い。