Anti-vascular diseases approach through the analysis of vascular-bed dependent diversity and activation

2017 Fiscal Year Final Research Report

• Project/Area Number: 26290035
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kumamoto University (2015-2017); The University of Tokyo (2014)
• Principal Investigator: Minami Takashi 熊本大学, 生命資源研究・支援センター, 教授 (00345141)
• Co-Investigator(Renkei-kenkyūsha): KANKI Yasuharu 東京大学, アイソトープ総合センター, 助教 (00534869)
• Research Collaborator: ABURATANI Hiroyuki ; YAMASHITA Jun
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 血管内皮細胞 / 内皮分化 / ヒストンプロファイル / トランスクリプトーム / マスター転写因子 / 分化パイオニア因子 / エピゲノム制御 / ヒストンスイッチング

Outline of Final Research Achievements

Studies of the differentiation from mouse ES cells to endothelial cells (ECs) provide an excellent model for investigating the mechanisms underlying vascular development. Here, we analyzed the EC differentiation steps from ES cells and crucial epigenetic modifications unique to ECs by using the epigenomics and transcriptomics approach. We determined that Gata2/Fli1/Sox7,18 are EC-master regulators induced following expression of the EC-commitment pioneer factor, Etv2. These master regulator gene loci were repressed by H3K27me3 under the mesoderm period, but rapidly transitioned to the histone modification switching to H3K4me3 after treatment with VEGF. These regulators are indispensable not only for proper EC differentiation but also for blocking the commitment to other closely aligned lineages. Our detailed epigenetic analysis might provide an advanced model for understanding temporal regulation of chromatin signature and resulting gene expression profiles during EC commitment.

Free Research Field

血管生物学