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The regulation of lympho-hematopoiesis by bone marrow niches

Research Project

Project/Area Number 22390096
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

NAGASAWA Takashi  京都大学, 再生医科学研究所, 教授 (80281690)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsサイトカイン / 造血幹細胞 / ニッチ / 骨髄 / ケモカイン
Research Abstract

We generated mice that allowed selective ablation of CAR cells within bone marrow and determined the in vivo function of CAR cells as a niche for hematopoietic stem cells (HSCs) and lympho-hematopoietic progenitors. Short-term ablation of CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells in vivo severely impaired the production of SCF and CXCL12, and led to a marked reduction in cycling lymphoid and erythroid progenitors. HSCs from CAR cell-depleted mice were reduced in number and cell size, were more quiescent and had increased expression of early myeloid selector genes. Thus, CAR cells are the major producer of CXCL12 and SCF and are required for proliferation of HSCs and lymphoid and erythroid progenitors as well as maintenance of HSCs in an undifferentiated state.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2013 2012 2011 2010 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (21 results) (of which Invited: 8 results)

  • [Journal Article] CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance2013

    • Author(s)
      Greenbaum, A., Hsu, Y.M., Day, R.B., Schuettpel,z L.G., Christopher, M.J., Borgerding, J.N., Nagasawa, T., *Link, D.C.
    • Journal Title

      Nature

      Volume: 495 Issue: 7440 Pages: 227-230

    • DOI

      10.1038/nature11926

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral Nerve-Derived CXCL12 and VEGF-A Regulate the Patterning of Arterial Vessel Branching in Developing Limb Skin2013

    • Author(s)
      Li, W., Kohara, H., Uchida, Y., James, J.M., Soneji, K., Cronshaw, D.G., Zou, Y.R., Nagasawa, T., *Mukouyama, Y.S.
    • Journal Title

      Dev. Cell

      Volume: Dev. Cell Issue: 4 Pages: 359-371

    • DOI

      10.1016/j.devcel.2013.01.009

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution of mouse spermatogonial stem cell niches in culture2012

    • Author(s)
      Kanatsu-Shinohara, M., Inoue, K., Takashima, S.,Takehashi, M.,Ogonuki, N., Morimoto, H., Nagasawa, T., Ogura, A. and Shinohara, T
    • Journal Title

      Cell Stem Cell

      Volume: 11(4) Issue: 4 Pages: 567-578

    • DOI

      10.1016/j.stem.2012.06.011

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system.2012

    • Author(s)
      Nishiyama, C., Uesaka, T., Manabe, T., Yonekura, Y., Nagasawa, T., Newgreen, D.F., Young, H.M., *Enomoto, H.
    • Journal Title

      Nat. Neurosci.

      Volume: 15(9) Issue: 9 Pages: 1211-1218

    • DOI

      10.1038/nn.3184

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development2012

    • Author(s)
      Sasaki, K. Hoshino, T. Sugiyama, C. Yamazaki, T. Yano, A. Iizuka, H. Hemmi, T. Tanaka, M. Saito, M. Sugiyama, Y. Fukuda, T. Ohta, K. Sato, A. Ainai, T. Suzuki, H. Hasegawa, N. Toyama-Sorimachi, H. Kohara, T. Nagasawa, T. Kaisho
    • Journal Title

      Blood

      Volume: 120 Issue: 24 Pages: 4733-4743

    • DOI

      10.1182/blood-2012-06-436527

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Endothelial Antigen ESAM Monitors Hematopoietic Stem Cell Status between Quiescence and Self-Renewal.2012

    • Author(s)
      Sudo, T.
    • Journal Title

      J. Immunol.

      Volume: 189 Issue: 1 Pages: 200-210

    • DOI

      10.4049/jimmunol.1200056

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive Plasmacytoid Dendritic Cell Migration to the Splenic White Pulp Is Cooperatively Regulated by CCR7- and CXCR4-Mediated Signaling.2012

    • Author(s)
      Umemoto, E.
    • Journal Title

      J. Immunol.

      Volume: 189 Issue: 1 Pages: 191-199

    • DOI

      10.4049/jimmunol.1200802

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.2012

    • Author(s)
      Murata, K.
    • Journal Title

      PLoS One.

      Volume: 7 Issue: 5 Pages: 237-44

    • DOI

      10.1371/journal.pone.0037163

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellul- ar matrix protein Tenascin-C is req- uired in the bone marrow microenvio- nment primed for hematopoietic rege- neration2012

    • Author(s)
      Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasa- wa T, Suda T, Kubota Y
    • Journal Title

      Blood

      Volume: 119 Issue: 23 Pages: 5429-5437

    • DOI

      10.1182/blood-2011-11-393645

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow niches for hematopoietic stem cells and immune cells.2012

    • Author(s)
      Sugiyama, T.
    • Journal Title

      Inflamm. Allergy Drug Targets

      Volume: 11 Issue: 3 Pages: 201-206

    • DOI

      10.2174/187152812800392689

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow niches for hematopoietic stem cells and immune cells2012

    • Author(s)
      Sugiyama, T., Nagasawa, T.
    • Journal Title

      Inflamm.Allergy Drug Targets

      Volume: (in press)

    • NAID

      120004287995

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of hematopoietic stem cells by the bone marrow stromal niche : the role of reticular cells2011

    • Author(s)
      Nagasawa, T., Omatsu, Y., Sugiyama, T.
    • Journal Title

      Trends Immunol.

      Volume: 32 Issue: 7 Pages: 315-320

    • DOI

      10.1016/j.it.2011.03.009

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emergency evacuation! Hematopoietic niches induce cell exit in infection2011

    • Author(s)
      Sugiyama, T., Nagasawa, T.
    • Journal Title

      Immunity

      Volume: 34 Issue: 4 Pages: 463-465

    • DOI

      10.1016/j.immuni.2011.04.009

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero2011

    • Author(s)
      Kubota Y, Takubo K, Hirashima M, Nagoshi N, Kishi K, Sano K, Murakami M, Ema M, Omatsu Y, Takahashi S, Nagasawa T, Shibuya M, Okano H, Suda T
    • Journal Title

      J Exp Med

      Volume: 208 Issue: 5 Pages: 949-960

    • DOI

      10.1084/jem.20102187

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL12-CXCR4 chemokine signaling is essential for NK cell development in adult mice.2011

    • Author(s)
      Noda, M.
    • Journal Title

      Blood

      Volume: VOL.117 Pages: 451-458

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development.2011

    • Author(s)
      Lei, Y.
    • Journal Title

      J.Exp.Med.

      Volume: VOL.208 Pages: 383-394

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells.2011

    • Author(s)
      Hiratsuka, S.
    • Journal Title

      Proc.Natl.Acad.Sci.U S A.

      Volume: VOL.108 Pages: 302-307

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL12-CXCR4 chemokine signaling is essential for NK cell development in adult mice.2010

    • Author(s)
      Noda, M., Omatsu, Y., Sugiyama, T., Oishi, S., Fujii, N., and *Nagasawa, T.
    • Journal Title

      Blood

      Volume: 117 Issue: 2 Pages: 451-458

    • DOI

      10.1182/blood-2010-04-277897

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche.2010

    • Author(s)
      Omatsu,Y., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno, K., *Nagasawa, T
    • Journal Title

      Immunity

      Volume: 33(3) Issue: 3 Pages: 2010-2010

    • DOI

      10.1016/j.immuni.2010.08.017

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche.2010

    • Author(s)
      Omatsu, T.
    • Journal Title

      Immunity

      Volume: VOL.33 Pages: 387-399

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow graft-versus-host disease : early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation.2010

    • Author(s)
      Shono, Y.
    • Journal Title

      Blood

      Volume: VOL.115 Pages: 5401-5411

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dock 180 is a rac activator that regulates cardiovascular development by acting downstream of CXCR4.2010

    • Author(s)
      Sanematsu, F.
    • Journal Title

      Circ.Res.

      Volume: VOL.107 Pages: 1102-1105

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Lymphocyte development "The adipo-osteogenic progenitors with long processes function as niches for hematopoietic stem and progenitor cells"2012

    • Author(s)
      T. Nagasawa
    • Organizer
      第41回日本免疫学会学術集会 シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2012-12-05
    • Related Report
      2012 Final Research Report
  • [Presentation] Adipo-osteogenic progenitors function as niches for hematopoietic stem and progenitor cells in the marrow2012

    • Author(s)
      T. Nagasawa
    • Organizer
      The 9th Nikko International Symposium 2012, Understanding complex network systems in disease biology.
    • Place of Presentation
      Tochigi
    • Year and Date
      2012-10-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Bone marrow niches controlling behavior of hematopoietic stem and progenitor cells2012

    • Author(s)
      長澤丘司
    • Organizer
      The 21st Hot Spring Harbor Symposium jointly with 9th Global COE international Symposium
    • Place of Presentation
      九州大学(福岡県)(招待講演)
    • Year and Date
      2012-01-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Bone marrow niches controlling behavior of hematopoietic stem and progenitor cells2012

    • Author(s)
      T. Nagasaw
    • Organizer
      The 21st Hot Spring Harbor Symposium jointly with 9th Global COE international Symposium; Cell Migration in Biology and Medicine
    • Place of Presentation
      Fukuoka
    • Related Report
      2012 Final Research Report
  • [Presentation] Adipo-osteogenic progenitors constitute reticular niches for hematopoietic stem and progenitor cells2011

    • Author(s)
      T. Nagasawa
    • Organizer
      The 23th Korean Society of Bone Metabolism Autumn Scientific Congress, Satellite Symposium:Bone and Hematopoietic System
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] Adipo-osteogenic progenitors constitute reticular niches for hematopoietic stem and progenitor cells2011

    • Author(s)
      長澤丘司
    • Organizer
      The 23th Korean Sciety of Bone Metabolism Autumn Scientific Congress
    • Place of Presentation
      ソウル(韓国)(招待講演)
    • Year and Date
      2011-11-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] CXCL12 and reticular niches for hematopoietic stem and progenitor cells2011

    • Author(s)
      長澤丘司
    • Organizer
      40th Annual Scientific Meeting of the ISEH Society for Hematology and Stem Cells
    • Place of Presentation
      バンクーバー(カナダ)(招待講演)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Bone marrow niches for hematopoietic stem and progenitor cells2011

    • Author(s)
      長澤丘司
    • Organizer
      日本炎症・再生医学会
    • Place of Presentation
      国立京都国際会館(京都府)(招待講演)
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] CXCL12 and reticular niches for hematopoietic stem and progenitor cells2011

    • Author(s)
      T. Nagasawa
    • Organizer
      40th Annual Scientific Meeting of the ISEH-Society for Hematology and Stem Cells, Break out session: Microenvironment.
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2012 Final Research Report
  • [Presentation] The chemokine CXCL12 and niches for hematopoietic stem cells and immune cells2010

    • Author(s)
      T.Nagasawa
    • Organizer
      14th International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] The chemokine CXCL12 and bone marrow niches for hematopoietic stem cells (HSCs) and immune cells.2010

    • Author(s)
      T.Nagasawa
    • Organizer
      3rd International Conference on Osteoimmunology.
    • Place of Presentation
      Fira, Santorini, Greece
    • Year and Date
      2010-06-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] The chemokine CXCL12 and niches for hematopoietic stem cells and immune cells.2010

    • Author(s)
      T. Nagasawa
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      Kobe
    • Related Report
      2012 Final Research Report
  • [Presentation] The chemokine CXCL12 and bone marrow niches for HSCs and immune cells2010

    • Author(s)
      T. Nagasawa
    • Organizer
      The 3rd International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems
    • Place of Presentation
      Fira, Greece
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨髄の造血幹細胞ニッシェと脂肪・骨前駆細胞CAR細胞

    • Author(s)
      長澤 丘司
    • Organizer
      第118回日本解剖学会総会・全国学術集会  シンポジウム 骨髄幹細胞ニッチと神経―免疫―内分泌クロストーク
    • Place of Presentation
      サンポートホール高松・かがわ国際会議場・高松
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The adipo-osteogenic progenitors with long processes function as niches for hematopoietic stem and progenitor cells

    • Author(s)
      T. Nagasawa
    • Organizer
      第41回日本免疫学会学術集会 シンポジウム
    • Place of Presentation
      神戸国際会議場・神戸
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 免疫担当細胞の産生と造血幹細胞・前駆細胞ニッシェ

    • Author(s)
      長澤 丘司
    • Organizer
      第41回日本免疫学会学術集会  レビュートーク
    • Place of Presentation
      神戸国際会議場・神戸
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Adipo-osteogenic progenitors function as niches for hematopoietic stem and progenitor cells in the marrow

    • Author(s)
      T. Nagasawa
    • Organizer
      The 9th Nikko International Symposium 2012, Understanding complex network systems in disease biology.
    • Place of Presentation
      Jich Medical University, Shimotsuke, Tochigi
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 骨髄の脂肪・骨前駆細胞 CAR細胞と造血幹細胞ニッシェ

    • Author(s)
      長澤 丘司
    • Organizer
      第30回 日本骨代謝学会学術集会 カレント コンセプト1 骨髄とがん細胞
    • Place of Presentation
      京王プラザホテル・東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 骨髄の造血幹細胞・造血ニッシェ

    • Author(s)
      長澤 丘司
    • Organizer
      第33回 日本炎症・再生医学会 シンポジウム 炎症と骨・骨髄
    • Place of Presentation
      ホテル日航福岡・福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 骨髄の微小環境(ニッシェ)による造血幹細胞と造血の制御

    • Author(s)
      長澤 丘司
    • Organizer
      第12回 日本加齢医学会総会 シンポジウム 24
    • Place of Presentation
      パシフィコ横浜会議センター・横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 骨髄の脂肪・骨前駆細胞CAR細胞と造血幹細胞ニッシェ

    • Author(s)
      長澤 丘司
    • Organizer
      第101回 日本病理学会総会 ワークショップ 造血幹細胞の病理:最先端研究から診断まで。
    • Place of Presentation
      京王プラザホテル・東京
    • Related Report
      2012 Annual Research Report
    • Invited

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Published: 2010-08-23   Modified: 2019-07-29  

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