Role of Sox17 family proteins in hematopoiesis at midgestation of mouse embryos

• Project/Area Number: 23570250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NOBUHISA Ikuo 東京医科歯科大学, 難治疾患研究所, 准教授 (40332879)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Sox17 / AGM / hematopoiesis

Research Abstract

During mouse development, definitive hematopoiesis is first detected in the aorta-gonad-mesonephros (AGM) region at around embryonic day 10.5 (E10.5), which exhibits intra-aortic cell clusters (IACCs). These clusters are known to contain hematopoietic stem cells (HSCs). It is unclear how the cells in such clusters maintain their HSC phenotype. We found that a transcription factor, Sox17, and other F-group (SoxF) proteins, Sox7 and Sox18, were expressed in E10.5 IACCs. Overexpression of any of these SoxF proteins in IACCs led to consistent formation of cell clusters in vitro during several passages of cocultures with stromal cells. Sox17-transduced cells retained a long-term bone marrow reconstitution activity in vivo. Shutdown of exogenously introduced Sox17 gene expression resulted in immediate hematopoietic differentiation. These results indicate that SoxF proteins, especially Sox17, contribute to the maintenance of cell clusters containing HSCs in the midgestation AGM region.

Research Products

• [Journal Article] Sox17-mediated maintenance of fetal intra-aortic hematopoietic cell clusters. (2014)
  • Author(s): 35. Nobuhisa I, Osawa M, Uemura M, Kishikawa Y, Anani M, Harada K, Takaki H, Saito K, Kanai-Azuma M, Kanai Y, Iwama A, Taga T.
  • Journal Title: Mol. Cell. Biol. Volume: -
  • Peer Reviewed
• [Journal Article] Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice (2013)
  • Author(s): Uemura. Mami., Ozawa A. Nagala T. Kurosawa K., Tsurukawa. K., Nobuhisa I., Taka T. Mara. K., Kudo, A., Kawakami. H., Saijoh. Y. Kurohmaru M. Kanai, Azuma. M., Kanai. Yoshiakira.
  • Journal Title: Development Volume: 140 Issue: 3 Pages: 639-648
  • DOI: 10.1242/dev.086702
  • Peer Reviewed
• [Journal Article] CD45 low c-Kit high cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region (2012)
  • Author(s): Ikuo Nobuhisa
  • Journal Title: Experimental Cell Research Volume: 318 Issue: 6 Pages: 705-715
  • DOI: 10.1016/j.yexcr.2012.01.017
  • Peer Reviewed
• [Journal Article] CD45lowc-Kithigh cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region. (2012)
  • Author(s): Nobuhisa et al
  • Journal Title: Exp. Cell Res. Volume: 318(6)
  • Peer Reviewed
• [Journal Article] Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression (2011)
  • Author(s): Shoutarou Yamasaki
  • Journal Title: Development Growth & Differentiation Volume: 53 Issue: 7 Pages: 870-877
  • DOI: 10.1111/j.1440-169x.2011.01293.x
  • Peer Reviewed
• [Journal Article] Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression. (2011)
  • Author(s): Yamasaki et al
  • Journal Title: Develop. Growth Differ. Volume: 53(7) Pages: 870-877
  • Peer Reviewed
• [Journal Article] Sox17-mediated maintenance of fetal intra-aortic hematopoietic cell clusters
  • Author(s): Nobuhisa I, Osawa M, Uemura M, Kishikawa Y, Anani M, Harada K, Takaki H, Saito K, Kanai-Azuma M, Kanai Y, Iwama A, Taga T
  • Journal Title: Mol Cell Biol Volume: (in press)
  • Peer Reviewed
• [Presentation] Analysis of recipients transplantated with the bone marrow cells of Sox17-transduced cells-transplanted mice (2013)
  • Author(s): 信久幾夫, 大澤光次郎, 原田果歩, Maha Anani, 齋藤清香, 高木春奈, 岩間厚志, 田賀哲也
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Introduction of Sox17 in the aorta-gonad-mesonephros-derived hematopoietic cells leads to increased common myeloid progenitors in transplanted mice (2013)
  • Author(s): 信久幾夫, 大澤光次郎, 上村麻実, 原田果歩, Maha Anani, 齋藤清香, 高木春奈, 金井正美, 金井克晃, 岩間厚志, 田賀哲也
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Thrombopoietin contributes to formation and maintenance of hematopoietic progenitor cell-containing cell clusters in the aorta-gonad-mesonephros region (2013)
  • Author(s): 原田果歩、信久幾夫、Maha Anani、齋藤清香、田賀哲也
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region by Sox17 (2013)
  • Author(s): 信久幾夫
  • Organizer: The 8th International Symposium of the Institute Network
  • Place of Presentation: 京都
• [Presentation] Sox17 protein-mediated maintenance of cells with stem cell phenotype in the hematopoietic cell clusters in the fetal AGM region (2013)
  • Author(s): 信久幾夫, 大澤光次郎, 上村麻実, 岸川陽子, Maha Anani, 原田果歩, 高木春奈, 金井正美, 金井克晃, 岩間厚志, 田賀哲也
  • Organizer: 第11回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] Sox17 protein-mediated maintenance of cells with stem cell phenotype in the hematopoietic cell clusters in the fetal AGM region. (2013)
  • Author(s): Nobuhisa I., et al
  • Organizer: The 11th Stem Cell Research Symposium.
  • Place of Presentation: 東京大学 伊藤国際学術センター
• [Presentation] Maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region by Sox17. (2013)
  • Author(s): Nobuhisa I.
  • Organizer: The 8th International Symposium of the Institute Network.
  • Place of Presentation: 京都大学 芝蘭会館
• [Presentation] Introduction of Sox17 in the aorta-gonad-mesonephros-derived hematopoietic cells leads to increased common myeloid progenitors in transplanted mice. (2013)
  • Author(s): Nobuhisa I., et al
  • Organizer: The 36th Annual Meeting of the Molecular Biology Society of Japan.
  • Place of Presentation: 神戸国際展示場
• [Presentation] Thrombopoietin contributes to formation and maintenance of hematopoietic progenitor cell-containing cell clusters in the aorta-gonad-mesonephros region. (2013)
  • Author(s): Harada K., Nobuhisa I., et al
  • Organizer: The 36th Annual Meeting of the Molecular Biology Society of Japan.
  • Place of Presentation: 神戸国際展示場
• [Presentation] Analysis of recipients transplantated with the bone marrow cells of Sox17-transduced cells-transplanted mice. (2013)
  • Author(s): Nobuhisa I., et al
  • Organizer: Annual Meeting of the Japan Society for Immunology.
  • Place of Presentation: 千葉 幕張メッセ
• [Presentation] Hematopoietic cell clusters present in the aorta-gonad-mesonephros region exhibited long-term repopulating ability by Sox17-expression (2012)
  • Author(s): 信久幾夫, 大澤光次郎, 上村麻実, 岸川陽子, Maha Anani, 原田果歩, 高木春奈, 金井正美, 金井克晃, 岩間厚志, 田賀哲也
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Hematopoietic cell clusters from the aorta-gonad-mesonephros region exhibited long-term repopulating ability by overexpression of Sox17 (2012)
  • Author(s): 信久幾夫, 大澤光次郎, 原田果歩, 高木春奈, 岩間厚志, 田賀哲也
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] SOX-F FAMILY PROTEINS HAVE ROLES IN THE MAINTAINANCE OF IMMATURE PHENOTYPE OF THE HEMATOPOIETIC CELL CLUSTERS IN THE AORTA-GONAD-MESONEPHROS REGION OF MOUSE EMBRYOS (2012)
  • Author(s): 信久幾, 大澤光次郎, 上村麻実, 岸川陽子, Maha Anani, 原田果歩, 高木春奈, 宮東明彦, 金井正美, 金井克晃, 岩間厚志, 田賀哲也
  • Organizer: The 10^<th> Annual Meeting of International Society for Stem Cell Research
  • Place of Presentation: 横浜
• [Presentation] Sox-F family proteins have roles in the maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region of mouse embryos. (2012)
  • Author(s): Nobuhisa I
  • Organizer: The 10th Annual Meeting of International Society for Stem Cell Research
  • Place of Presentation: パシフィッコ横浜
• [Presentation] Hematopoietic cell clusters from the aorta-gonad-mesonephros region exhibited long-term repopulating ability by overexpression of Sox17. (2012)
  • Author(s): Nobuhsa I
  • Organizer: 第41回 日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Hematopoietic cell clusters present in the aorta-gonad-mesonephros region exhibited long-term repopulating ability by Sox17-expression. (2012)
  • Author(s): Nobuhisa I
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region by SoxF family proteins (2011)
  • Author(s): 信久幾夫, 岸川陽子, 上村麻実, Maha Anani, 金井正美, 金井克晃, 田賀哲也
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] SoxF family proteins have roles in maintenance of immature phenotype of hematopoietic progenitors in the aorta-gonad-mesonephros region (2011)
  • Author(s): 信久幾夫, 岸川陽子, Maha Anani, 田賀哲也
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Role of SoxF family proteins in the maintenance of immature phenotype of hematopoietic progenitors in the aorta-gonad-mesonephros region (2011)
  • Author(s): 信久幾夫, 岸川陽子, 上村麻実, Maha Anani, Gomaa Ahmed, 金井正美, 金井克晃, 田賀哲也
  • Organizer: 第9回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] Role of SoxF family proteins in the maintenance of immature phenotype of hematopoietic progenitors in the aorta-gonad-mesonephros region. (2011)
  • Author(s): Ikuo Nobuhisa
  • Organizer: 第9回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー
• [Presentation] SoxF family proteins have roles in maintenance of immature phenotype of hematopoietic progenitors in the aorta-gonad-mesonephros region. (2011)
  • Author(s): Ikuo Nobuhisa
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] Maintenance of immature phenotype of the hematopoietic cell clusters in the aorta-gonad-mesonephros region by SoxF family proteins. (2011)
  • Author(s): Ikuo Nobuhisa
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/scr/index.html
• [Remarks] 東京医科歯科大学 難治疾患研究所 幹細胞制御分野 HP
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• [Remarks] プレス通知資料（研究成果）
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20140423.pdf
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/scr/index.html