The humatopoietic stem cell induction from human embryonic stem cells

• Project/Area Number: 24591381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University (2013-2014); Chiba University (2012)
• Principal Investigator: OSAWA Mitsujiro 京都大学, iPS細胞研究所, 特定助教 (70546770)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 造血幹細胞 / human ES / ヒト多能性幹細胞 / 造血発生 / hESCs / SOX17

Outline of Final Research Achievements

To understand the molecular basis of hematopoietic differentiation from human pluripotent stem cell included human embryonic stem cells and human induced pluripotent stem cells, we first analyzed a hematopoietic phenotype and gene expression on human ES-derived hematopoietic progenitor cells. As a result, hematopoietic progenitor cells with long-term culture showed developmental maturation of hematopoietic. We also evaluated the effects of overexpression of key molecules predicted to support the generation and maturation of HSCs. Among genes tested, we found that only SOX17 plays a critical role in priming hemogenic potential of endothelial cells.

Research Products

• [Journal Article] Sox17-ediated Maintenance of Fetal Intra-ortic Hematopoietic Cell Clusters (2014)
  • Author(s): Nobuhisa. Ikuo., Ozawa. M., Uemura. M., Kishikawa. Y., Azumi. M. Harada K. Takagi M Saito. K., Kanai-Azuma M. Kanai. Y Iwama. A. Tetsuya.
  • Journal Title: MCB Volume: (印刷中) Issue: 11 Pages: 1976-90
  • DOI: 10.1128/mcb.01485-13
  • Peer Reviewed / Open Access
• [Journal Article] Sox17 as a candidate regulator of myeloid restricted differentiation potential. (2014)
  • Author(s): Anani M, Nobuhisa I, Osawa M, Iwama A, Harada K, Saito K, Taga T
  • Journal Title: Dev. Growth Differ. Volume: 56 Issue: 6 Pages: 469-479
  • DOI: 10.1111/dgd.12147
  • NAID: 40020174678
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Manipulation of hematopoietic stem cells for regenerative medicine (2014)
  • Author(s): Nakajima-Takagi Y, Osawa M, Iwama A
  • Journal Title: The Anatomical Record Volume: 297 Issue: 1 Pages: 111-120
  • DOI: 10.1002/ar.22804
  • Peer Reviewed
• [Journal Article] Role of SOX17 in hematopoietic development from human embryonic stem cells. (2013)
  • Author(s): Nakajima-Takagi Y, Osawa M, Oshima M, Takagi H, Miyagi S, Endoh M, Endo TA, Takayama N, Eto K, Toyoda T, Koseki H, Nakauchi H, Iwama A.
  • Journal Title: Blood. Volume: 121 Issue: 3 Pages: 447-58
  • DOI: 10.1182/blood-2012-05-431403
  • Peer Reviewed
• [Journal Article] Compromised hematopoiesis and increased DNA damage following non-lethal ionizing radiation of a human hematopoietic system reconstituted in immunodeficient mice. (2013)
  • Author(s): Wang C, Nakamura S, Oshima M, Mochizuki-Kashio M, Nakajima-Takagi Y, Osawa M, Kusunoki Y, Kyoizumi S, Imai K, Nakachi K, Iwama A
  • Journal Title: Int J Radiat Biol Volume: 89 Issue: 2 Pages: 132-137
  • DOI: 10.3109/09553002.2013.734947
  • Peer Reviewed
• [Presentation] Sustained expression of Sox17 in AGM-derived hematopoietic stem/progenitor cells maintain the self-renewal capacity and the hematopoietic ability to produce myeloid progenitors (2014)
  • Author(s): Maha Anani, Ikuo Nobuhisa, Mitsujiro Osawa, Atsushi Iwama, Kaho Harada, Kiyoka Saito, Tetsuya Taga
  • Organizer: 免疫学会（第43回）
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Sustained expression of Sox17 in the aorta-gonad-mesonephros-derived hematopoietic cells maintain the self-renewal capacity and the hematopoietic ability to produce myeloid progenitors (2014)
  • Author(s): Maha Anani, Ikuo Nobuhisa, Mitsujiro Osawa, Atsushi Iwama, Kaho Harada, Kiyoka Saito, Tetsuya Taga
  • Organizer: 分子生物学会（第37回）
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Sox17-transduction imparts fetal hematopoietic cells with the myeloid-restricted differentiation potential (2014)
  • Author(s): Maha Anani, Ikuo Nobuhisa, Mitsujiro Osawa, Atsushi Iwama, Kaho Harada, Kiyoka Saito, Tetsuya Taga
  • Organizer: 幹細胞シンポジウム（第12回）
  • Place of Presentation: 九州大学医学部・百年講堂（福岡）
  • Year and Date: 2014-05-30 – 2014-05-31
• [Presentation] Sox17 protein-mediated maintenance of cells with stem cell phenotype in the hematopoietic cell clusters in the fetal AGM region (2013)
  • Author(s): 1) Ikuo Nobuhisa, Mitsujiro Osawa, Mami Uemura, Yoko Kishikawa, Maha Anani, Kaho Harada, Haruna Takagi, Masami Kanai-Azuma, Yoshiakira Kanai, Atsushi Iwama, Tetsuya Taga.
  • Organizer: The 11th Stem Cell Research Symposium
  • Place of Presentation: Tokyo
• [Presentation] Introduction of Sox17 in the aorta-gonad-mesonephros-derived hematopoietic cells leads to increased common myeloid progenitors in transplanted mice (2013)
  • Author(s): 2) Ikuo Nobuhisa, Mitsujiro Osawa, Mami Uemura, Yoko Kishikawa, Maha Anani, Kaho Harada, Haruna Takagi, Masami Kanai-Azuma, Yoshiakira Kanai, Atsushi Iwama, Tetsuya Taga
  • Organizer: The 36th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe
• [Presentation] Analysis of recipients transplantated with the bone marrow cells of Sox17-transduced cells-transplanted mice (2013)
  • Author(s): 3) Ikuo Nobuhisa, Mitsujiro Osawa, Kaho Harada, Maha Anani, Kiyoka Sito Haruna Takagi, Atsushi Iwama, Tetsuya Taga
  • Organizer: Annual Meeting of the Japan Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] The Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2013)
  • Author(s): Osawa M, Nakajima Y, Oshima M, Takagi H and Iwama A
  • Organizer: Keystone Symposium: Hematopoiesis
  • Place of Presentation: Steamboat Springs, USA
• [Presentation] The Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2012)
  • Author(s): Osawa M, Nakajima Y, Oshima M, Takagi H, Endoh M, Endo T and Iwama A
  • Organizer: The 10th Stem Cell Research Symposium
  • Place of Presentation: Awaji, Japan
• [Presentation] Inhibition of TGF-beta signaling in the early mesoderm stage promotes the development of hematopoietic progenitors from human embryonic stem cells (2012)
  • Author(s): Osawa M, Takagi H, Nakajima Y, Endoh M, Endo A.T and Iwama A
  • Organizer: The 10th International Society of Stem Cell Research, ISSCR
  • Place of Presentation: Yokohama, Japan
• [Presentation] The Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2012)
  • Author(s): Nakajima Y, Osawa M, Oshima M, Takagi H and Iwama A
  • Organizer: The 10th International Society of Stem Cell Research, ISSCR
  • Place of Presentation: Yokohama, Japan
• [Presentation] The Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2012)
  • Author(s): Nakajima Y, Osawa M, Oshima M, Takagi H, Endoh M, Endo A.T, Toyoda T, Koseki H and Iwama A
  • Organizer: The 72th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto, Japan
• [Presentation] ヒト胚性幹細胞からの造血発生におけるSOX17の役割
  • Author(s): 大澤光次郎
  • Organizer: 東京医科歯科大学駿河台国際シンポジウム（12th Surugadai International Symposium）
  • Place of Presentation: 東京
  • Invited
• [Book] ES/iPS細胞 実験スタンダード (2014)
  • Author(s): 鈴木直也、大澤光次郎
  • Total Pages: 10
  • Publisher: 羊土社