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Characterization and exploration of bone marrow niche regulators for hematopoietic stem cells

Research Project

Project/Area Number 23390256
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

HARA Takahiko  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, プロジェクトリーダー(参事研究員) (80280949)

Co-Investigator(Kenkyū-buntansha) KITAJIMA Kenji  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (10346132)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords造血幹細胞 / 骨髄ニッチ / ニッチ / CXCL14 / ES細胞 / ES細胞分化 / CXCL12 / CMG-1 / Lhx2 / 急性骨髄性白血病
Research Abstract

To understand how hematopoietic stem cells (HSCs) interact with bone marrow niche, we investigated functions of chemokine CXCL14 and cilia protein CMG-1, and searched for downstream effector molecules of the HSC-acting transcription factor Lhx2. We discovered that CXCL14 binds to CXCR4 with high affinity and completely inhibits the CXCL12-mediated migration of hematopoietic progenitor cells. However, number and frequency of bone marrow HSCs in CXCL14 knockout mice were similar as those in wild type mice. Same thing was true in bone marrows of HSC-specific CMG-1 conditional knockout mice. Lastly, we searched for membrane proteins that are relevant to the undifferentiated status of HSCs by using an Lhx2-trigerred HSC expansion culture of ES cells. As a result, we identified several candidate genes such as Biglycan, Esam1, and Jam3.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (47 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 12 results) Presentation (27 results) (of which Invited: 5 results) Remarks (4 results)

  • [Journal Article] CXCL14 antagonizes the CXCL12-CXCR4 signaling axis2014

    • Author(s)
      T. Hara and K. Tanegashima
    • Journal Title

      BioMol. Concepts

      Volume: 5 Pages: 167-173

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCL14 antagonizes the CXCL12-CXCR4 signaling axis.2014

    • Author(s)
      T. Hara and K. Tanegashima
    • Journal Title

      BioMol. Concepts

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic progenitor cells derived from mouse embryonic stem cells2013

    • Author(s)
      K. Kitajima, M. Kawaguchi, M. Iacovino, M. Kyba, and T. Hara
    • Journal Title

      Stem Cells

      Volume: 31 Pages: 2680-2689

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors2013

    • Author(s)
      K. Tanegashima, K. Tsuji, K. Suzuki, A. Shigenaga, A. Otaka, and T. Hara
    • Journal Title

      FEBS Letters

      Volume: 587 Pages: 3770-3775

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCL14 is a natural inhibitor of the CXCL12-CXCR4 signaling axis2013

    • Author(s)
      K. Tanegashima, K. Suzuki, Y. Nakayama, K. Tsuji, A. Shigenaga, A. Otaka, and T. Hara
    • Journal Title

      FEBS Letters

      Volume: 587 Pages: 1731-1735

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of antagonistic peptide for putative CXCL14 receptor protein and their identification2013

    • Author(s)
      K. Tsuji, K. Tanegashima, A. Shigenaga, K. Aihara, M. Denda, H. Ding, T. Hara, and A. Otaka
    • Journal Title

      Peptide Science

      Pages: 31-32

    • NAID

      10031161538

    • Related Report
      2013 Final Research Report
  • [Journal Article] Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic progenitor cells derived from mouse embryonic stem cells.2013

    • Author(s)
      K. Kitajima, M. Kawaguchi, M. Iacovino, M. Kyba, and T. Hara
    • Journal Title

      Stem Cells

      Volume: 31 Issue: 12 Pages: 2680-2689

    • DOI

      10.1002/stem.1500

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors2013

    • Author(s)
      K. Tanegashima, K. Tsuji, K. Su zuki, A. Shigenaga, A. Otaka, and T. Hara
    • Journal Title

      FEBS Letters

      Volume: 587 Issue: 23 Pages: 3770-3775

    • DOI

      10.1016/j.febslet.2013.10.017

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL14 is a natural inhibitor of the CXCL12-CXCR4 signaling axis2013

    • Author(s)
      K. Tanegashima, K. Suzukia, Y. Nakayama, K. Tsuji, A. Shigenaga, A. Otaka, and T. tiara
    • Journal Title

      FEBS Letters

      Volume: 587 Issue: 12 Pages: 1731-1735

    • DOI

      10.1016/j.febslet.2013.04.046

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pleiotropic functions of the CXC-type chemokine CXCL14 in mammals2012

    • Author(s)
      T. Hara and K. Tanegashima
    • Journal Title

      J. Biochem

      Volume: 151 Pages: 469-476

    • NAID

      10031166086

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ES細胞・iPS細胞から機能的な血液細胞を作り出す方法2012

    • Author(s)
      原孝彦, 北島健二
    • Journal Title

      実験医学(増刊号)

      Volume: 30 Pages: 1671-1676

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pleiotropic functions of the CXC-type chemokine CXCL14 in mammals.2012

    • Author(s)
      T. Hara and K. Tanegashima
    • Journal Title

      J. Biochem.

      Volume: 151 Issue: 5 Pages: 469-476

    • DOI

      10.1093/jb/mvs030

    • NAID

      10031166086

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ES細胞・iPS細胞から機能的な血液細胞を作り出す方法2012

    • Author(s)
      原 孝彦, 北島健二
    • Journal Title

      実験医学

      Volume: 30(増刊号) Pages: 1671-1676

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Directing migration of endothelial progenitor cells with applied DC electric fields2012

    • Author(s)
      Z.Zhao, L.Oin, B.Reid, J.Pu, T.Hara, M.Zhao
    • Journal Title

      Stem Cell Research

      Volume: 8 Issue: 1 Pages: 38-48

    • DOI

      10.1016/j.scr.2011.08.001

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx22011

    • Author(s)
      K.Kitajima, K.Minehata, K.Sakimura, T.Nakano, T.Hara
    • Journal Title

      Blood

      Volume: 117 Issue: 14 Pages: 3748-3758

    • DOI

      10.1182/blood-2010-07-298596

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] iPS細胞から造血幹細胞への分化誘導2011

    • Author(s)
      北島健二、原孝彦
    • Journal Title

      医学のあゆみ(増刊号)

      Volume: 239 Pages: 1397-1401

    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular mechanisms of the Lhx2-mediated generation of HSC-like cells from embryonic stem cells2013

    • Author(s)
      K. Kitajima, M. Kawaguchi, K. Miyashita, M. Iacovino, M. Kyba, and *T. Hara
    • Organizer
      2nd IGAKUKEN International Symposium on Hematopoietic Stem Cell Development
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-02-08
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] ケモカインCXCL14は, CXCL12-CXCR4シグナル経路を阻害する2013

    • Author(s)
      種子島幸祐, 鈴木健司, 辻耕平, 重永章, 大高章, 原孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] Gata2 はhemogenic endothelial cells からの血液細胞出芽を促進する2013

    • Author(s)
      川口真実, 北島健二, 原孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写制御因子Lhx2は急性Tリンパ芽球性白血病細胞の増殖を抑制する2013

    • Author(s)
      宮下和也, 北島健二, 原孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro induction of HSC-like cells from mouse ESCs/iPSCs by a transcription factor Lhx22013

    • Author(s)
      *K. Kitajima, M. Kawaguchi, K. Miyashita, and T. Hara
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms of the Lhx2-mediated generation of hematopoietic stem cell-like cells from murine ES/iPS cells2013

    • Author(s)
      K. Kitajima, M. Kawaguchi, K. Miyashita, M. Iacovino, M. Kyba, and *T. Hara
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic stem-like cell differentiation from mouse embryonic stem cells2013

    • Author(s)
      *K. Kitajima, M. Kawaguchi, M. Iacovino, M. Kyba, and T. Hara
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      本郷
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of The CXCL14 Receptor : CXCL14 is a Natural Inhibitor of The CXCL12/CXCR4 Axis2013

    • Author(s)
      K. Tanegashima, K. Suzuki, T. Nagasawa, and T. Hara
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      本郷
    • Related Report
      2013 Final Research Report
  • [Presentation] CXCL12-CXCR4軸を介した幹細胞誘引の調節因子2013

    • Author(s)
      *原孝彦, 種子島幸祐, 鈴木健司, 辻耕平, 重永章, 長澤丘司, 大高章
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Molecular mechanisms of the Lhx2-mediated generation of hematopoietic stem cell-like cells from murine ES/iPS cells.2013

    • Author(s)
      K. Kitajima, M. Kawaguchi, K. Miyashita, M. Iacovino, M. Kyba, ○T. Hara
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ケモカインCXCL14は、CXCL12-CXCR4シグナル経路を阻害する.2013

    • Author(s)
      種子島幸祐, 鈴木健司, 辻 耕平, 重永 章, 大高 章, 原 孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Lhx2 は筋脱分化因子 Msx1, Msx2 の発現を制御する.2013

    • Author(s)
      小高悠作, 田中貴代子, 北島健二, 松田良一, 原 孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Gata2 は hemogenic endothelial cells からの血液細胞出芽を促進する.2013

    • Author(s)
      川口真実, 北島健二, 原 孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 転写制御因子 Lhx2 は急性 T リンパ芽球性白血病細胞の増殖を抑制する.2013

    • Author(s)
      宮下和也, 北島健二, 原 孝彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Identification of The CXCL14 Receptor: CXCL14 is a Natural Inhibitor of The CXCL12/CXCR4 Axis.2013

    • Author(s)
      K. Tanegashima, K. Suzuki, T. Nagasawa, and T. Hara
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic stem-like cell differentiation from mouse embryonic stem cells.2013

    • Author(s)
      ○K. Kitajima, M. Kawaguchi, M. Iacovino, M. Kyba, and T. Hara
    • Organizer
      第11回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Induction of hematopoietic stem-like cells from mouse pluripotent stem cells by LIM-homeobox transcription factor Lhx22012

    • Author(s)
      *北島健二, 川口真実, 籾山和沙, M. Kyba, 原孝彦
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Lhx2の強制発現はマウスES細胞からの原始造血前駆細胞分化を促進する2012

    • Author(s)
      川口真実, 北島健二, M. Kyba, 原孝彦
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] Underlying mechanisms of the in vitro induction of hematopoietic stem cell-like cells from mouse embryonic stem cells by Lim-homeobox transcription factor, Lhx22012

    • Author(s)
      K. Kitajima, M. Kyba, and T. Hara
    • Organizer
      10th Annual Meeting of International Society for Stem Cell Research (ISSCR)
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Final Research Report
  • [Presentation] CXCL14 acts as a natural inhibitor for CXCL12/CXCR4 signaling2012

    • Author(s)
      *T. Hara, K. Tanegashima, K. Tsuji, K. Suzuki, Y. Nakayama, A. Shigenaga, T. Nagasawa, M. Mori, and A. Otaka
    • Organizer
      Gordon Research Conference "Chemotactic Cytokines"
    • Place of Presentation
      Ciocco, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of G protein coupled receptors which constitute the functional CXCL14 receptors2012

    • Author(s)
      鈴木健司, 種子島幸祐, 中山由紀, 重永章, 長澤丘司, 大高章, 森正明, 原孝彦
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Lhx2によるマウス多能性幹細胞から造血幹細胞への分化誘導2012

    • Author(s)
      北島健二, 川口真実, 籾山和沙, Michael Kyba, 原 孝彦
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Underlying mechanisms of the in vitro induction of hematopoietic stem cell-like cells from mouse embryonic stem cells by Lim-homeobox transcription factor, Lhx2.2012

    • Author(s)
      K. Kitajima, M. Kyba, and T. Hara
    • Organizer
      10th Annual Meeting of International Society for Stem Cell Research
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Effects of ectopic expression of LIM-homeobox transcription factor lhx2 on in vitro differentiation of ESCs/iPSCs2011

    • Author(s)
      北島健二, 原孝彦
    • Organizer
      第44回日本発生生物学会年会
    • Place of Presentation
      宜野湾
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivo analyses of mouse iPSC-derived HSC-like cells generated by enforced expression of LIM-homeobox transcription factor Lhx22011

    • Author(s)
      K. Kitajima and T. Hara
    • Organizer
      第9回幹細胞シンポジウム
    • Place of Presentation
      六本木
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivo analyses of mouse iPSC-derived HSC-like cells generated by enforced expression of LIM-homeobox transcription factor Lhx22011

    • Author(s)
      K.Kitajima, T.Hara
    • Organizer
      第9回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] FoxO1 is required for hemangioblast development in mice2011

    • Author(s)
      K.Minehata, K.Kitajima, M.Kyba, T.Hara
    • Organizer
      第9回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/stem-cell/

    • Related Report
      2013 Final Research Report
  • [Remarks] 東京都医学総合研究所 幹細胞プロジェクト

    • URL

      http://www.igakuken.or.jp/stem-cell/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京都医学総合研究所 幹細胞プロジェクト

    • URL

      http://www.igakuken.or.jp/stem-cell/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/stem-cell/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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