Epigenetic regulation during maturation of endothelial cell

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14914
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: TANAKA TORU 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (50806065)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 血管内皮細胞 / 転写制御 / エピジェネティクス

Outline of Final Research Achievements

Endothelial cells (ECs) mature into arterial and venous ECs, and then change gene expression. The differences in gene expression are important in vasculogenesis. However, the mechanisms of arterial/venous EC specific gene expression are poorly understood. In this study, I focused on epigenetic modification and investigated the molecular mechanism that produces the specificity of arterial and venous ECs. I found that the inhibitors of a particular histone modifier suppressed the arterial maturation of ECs and increased the expression of vein-specific genes. These data suggest that the histone modifier function is involved in the arterial maturation.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

動脈・静脈内皮細胞がそれぞれの特異性を持つことは正常な血管形成に不可欠である。内皮細胞の成熟においてエピゲノムがどのように規定され遺伝子発現を制御するかを理解することは血管形成の分子機構を知る重要な手がかりとなり、効率的な血管内皮細胞への分化誘導法の開発、再生医療への応用に繋がる。また、死因の上位を占める疾患（癌、心疾患、脳血管障害）には血管形成が関連しており、将来的にエピジェネティック修飾因子を標的とした治療薬が血管関連疾患の新規治療法への応用に役立つことが期待される。