The role of Foxo1 transcription factor in the regulation of vascular formation

• Project/Area Number: 24792237
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: TAMURA Kiyomi 熊本大学, 発生医学研究所, 助教 (90399973)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血管 / Foxo1 / 胚性幹細胞（ES細胞） / 転写因子 / 胚性幹細胞

Research Abstract

Transcription factor Forkhead box O1 (Foxo1) (-/-) mice fail to develop vascular structure and are embryonic lethal by E11. So, Foxo1 is essential for the vascular development. However the mechanism is unclear.
In vitro vessel-like structure formation of ES cells are the useful examination system for vascular formation. In this model, vascular endothelial cells (ECs) derived from wild type ES cells showed the long and thin elongated morphology, but Foxo1 (-/-) EC failed to elongate. And, wild type pericytes can associate with wild type EC. Foxo1 (-/-) cells show no-association between EC and pericytes. To identify the Foxo1 target genes that are responsible for the regulation of EC elongation, I analyzed gene expression profiles of ECs and rescue studies of putative target genes. As a result, I identified an putative target gene. Furthermore, analysis of EC specific Foxo1 expressing ES cells show that Foxo1 in EC regulates EC-pericyte association.

Research Products

• [Journal Article] Molecular pathways governing development of vascular endothelial cells from ES/ iPS cells. (2013)
  • Author(s): Tan KS, Tamura K, Lai MI, Veerakumarasivam A, Nakanishi Y, Ogawa M and Sugiyama D.
  • Journal Title: Stem Cell Rev. Volume: 9（5） Issue: 5 Pages: 586-98
  • DOI: 10.1007/s12015-013-9450-7
  • Peer Reviewed
• [Presentation] Regulation of vascular morphogenesis by Foxo1 transcription factor via phospho-myosin light chain (2014)
  • Author(s): 田村-辻 潔美, 坂本 比呂志, 小川 峰太郎
  • Organizer: 第2回 Inflammation and Regeneration Meeting
  • Place of Presentation: 品川プリンスホテル, 東京
• [Presentation] Regulation of vascular morphogenesis by Foxo1 transcription factor via phospho-myosin light chain (2014)
  • Author(s): 田村-辻 潔美, 坂本 比呂志, 小川 峰太郎
  • Organizer: 第2回 Inflammation and Regeneration Meeting
  • Place of Presentation: 東京, 品川プリンスホテル
• [Presentation] 休眠状態の血液幹細胞は, 転写因子 c-myb の発現レベルを低く保っている (2013)
  • Author(s): Hiroshi Sakamoto1, Naoki Takeda, Kiyomi Tsuji-Tamura, Saeka Hirota, Atsushi Hashiguchi, Tazir Ahmed and Minetaro Ogawa
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館, 札幌
• [Presentation] 転写因子Foxo1による血管内皮細胞の形態制御メカニズムの解析 (2013)
  • Author(s): 田村-辻 潔美, 坂本 比呂志, 小川 峰太郎
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会館, 京都
• [Presentation] 眠状態の血液幹細胞は、転写因子c-mybの発現レベルを低く保っている (2013)
  • Author(s): Hiroshi Sakamoto1, Naoki Takeda, Kiyomi Tsuji-Tamura, Saeka Hirota, Atsushi Hashiguchi, Tazir Ahmed and Minetaro Ogawa
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌, ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館
• [Presentation] 転写因子Ｆｏｘｏ１による血管内皮細胞の形態制御メカニズムの解析 (2013)
  • Author(s): 田村-辻 潔美、坂本 比呂志、小川 峰太郎
  • Organizer: 第34回 日本炎症・再生医学会
  • Place of Presentation: 京都, 国立京都国際会館
• [Presentation] Forkhead transcriptional factor 1 (Foxo1) regulates vascular endothelial cell morphology (2013)
  • Author(s): 田村清美
  • Organizer: 有馬５拠点ミーティング
  • Place of Presentation: 有馬兵衛向陽閣（有馬）
• [Presentation] Levels of the c-Myb Protein Indicate Repopulating Capacity in Long-Term Hematopoietic Stem Cells (2012)
  • Author(s): Hiroshi Sakamoto, Naoki Takeda, Kiyomi Tsuji-Tamura, Saeka Hirota and Ogawa Minetaro
  • Organizer: 2012 ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] Expression and function of c-Myb in hematopoietic stem cells (2012)
  • Author(s): Hiroshi Sakamoto, Naoki Takeda, Paloma Garcia, Kiyomi Tsuji-Tamura, Saeka Hirota, Jon Frampton and Minetaro Ogawa
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館, 京都
• [Presentation] 血管内皮細胞の形態制御に関与する転写因子Foxo1の標的因子の探索 (2012)
  • Author(s): 田村-辻 潔美, 坂本 比呂志, 小川 峰太郎
  • Organizer: 第33回日本炎症・再生医学
  • Place of Presentation: ホテル日航福岡, 福岡
• [Presentation] Expression and function of c-Myb in hematopoietic stem cells (2012)
  • Author(s): Hiroshi Sakamoto, Takeda Naoki, Paloma Garcia, Kiyomi Tsuji-Tamura, Saeka Hirota, Jon Frampton, Minetaro Ogawa
  • Organizer: 第10回幹細胞シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場, 淡路島
• [Presentation] Levels of the c-Myb Protein Indicate Repopulating Capacity in Long-Term Hematopoietic Stem Cells (2012)
  • Author(s): Hiroshi Sakamoto, Naoki Takeda, Kiyomi Tsuji-Tamura, Saeka Hirota1 and Ogawa Minetaro
  • Organizer: 2012 ASH (American society of hematology) Annual Meeting and Exposition
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] 転写因子c-mybの血液幹細胞における発現と機能 (2012)
  • Author(s): Hiroshi Sakamoto, Naoki Takeda, Paloma Garcia, Kiyomi Tsuji-Tamura, Saeka Hirota, Jon Frampton and Minetaro Ogawa
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 血管内皮細胞の形態制御に関与する転写因子Ｆｏｘｏ１の標的因子の探索 (2012)
  • Author(s): 田村-辻 潔美、坂本 比呂志、小川 峰太郎
  • Organizer: 第33回日本炎症・再生医学
  • Place of Presentation: ホテル日航福岡（福岡）
• [Presentation] Expression and function of c-Myb in hematopoietic stem cells (2012)
  • Author(s): Hiroshi Sakamoto, Takeda Naoki, Paloma Garcia, Kiyomi Tsuji-Tamura, Saeka Hirota, Jon Frampton, Minetaro Ogawa
  • Organizer: 第10回幹細胞シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場（淡路島）
• [Book] 微小環境の血液幹細胞への働きかけ-誕生から骨髄での維持まで, 実験医学増刊-臓器円環による生体恒常性のダイナミクス, 永井良三, 入來篤史/編 (2013)
  • Author(s): 坂本比呂志, 田村潔美, 小川峰太郎
  • Publisher: 羊土社
• [Book] 実験医学増刊-臓器円環による生体恒常性のダイナミクス, 微小環境の血液幹細胞への働きかけ─誕生から骨髄での維持まで (2013)
  • Author(s): 坂本比呂志, 田村潔美, 小川峰太郎
  • Publisher: 羊土社
• [Book] 実験医学増刊（臓器円環による生体恒常性のダイナミクス、永井良三、入來篤史／編）Vol.31 No.5 (2013)
  • Author(s): 坂本比呂志、田村潔美、小川峰太郎
  • Publisher: 羊土社