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Bone Marrow Microenvironments for Hematopoiesis

Research Project

Project/Area Number 15590344
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational University Corporation Tottori University

Principal Investigator

HAYASHI Shin-ichi  Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (50208617)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsBone marrow / Hematopoiesis / Osteoclast / B cell / Toll-like receptor / Lipopolysaccharide(LPS) / Tyrosine phosphatase / Embryonic stem(ES) cell / 髄外造血 / 幹細胞 / 造血支持細胞 / Notchシグナル / リポポリサッカライド
Research Abstract

1)Analysis of osteoclastogenesis for bone marrow formation :
Osteoclasts are hematopoietic cells, which participate in bone resorption and remodeling. Receptor activator of NF-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) are critical for development of osteoclasts. The Toll-like receptor(TLR) family shares some of the downstream signaling with RANK, however, the signaling via TLRs has never been reported to induce osteoclastogenesis without RANKL. We showed that significant numbers of mature osteoclasts were generated from protein tyrosine phosphatase SHP-1-defective me^v/me^v bone marrow cells in the presence of M-CSF and LPS, a TLR4 ligand without addition of RANKL in culture. The osteoclast precursors were present in the Kit-positive cell enriched fraction of BM cells. Although me^v/me^v bone marrow cells required a comparable concentration of RANKL or TNF-α as wild-type cells for the initiation of osteoclastogenesis, numbers of multinucleated osteoclasts in me^v/ … More me^v bone marrow cultures were significantly increased by the equivalent dose of RANKL or TNF-α in the presence of M-CSF. These results indicate that a defect of SHP-1 function not only accelerates physiological osteoclast development by RANKL/RANK, but also acquires an aberrant pathway for osteoclastogenesis by LPS.
2)Induction of hematopoiesis from blood-less embryonic stem (ES) cell line :
Transcription factor Tal-1 is essential for the specification of hematopoietic development. Mice lacking Tall fail to generate any hematopoietic precursors. Using our co-culture system with stromal cells, we demonstrate that enforced expression of the transcription factor PU.1 under tetracycline control in Tall-null ES cells rescues the development of osteoclasts and macrophage-like phagocytes expressing a macrophage restricted marker. Other hematopoietic lineage cells were not generated. Their development was dependent on M-CSF and RANKL. These results suggest that the expression of PU.1 is a critical event for osteoclastogenesis and that Tal-1 may lie upstream of PU.1 in a regulatory hierarchy during osteoclastogenesis. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (42 results)

All 2005 2004 2003 Other

All Journal Article (30 results) Book (2 results) Publications (10 results)

  • [Journal Article] Enforced expression of PU.1 rescues osteoclastogenesis from embryonic stem cells lacking Tal-12005

    • Author(s)
      Tsuneto, M., et al.
    • Journal Title

      Stem Cells 23

      Pages: 134-143

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation2005

    • Author(s)
      Yamazaki, H., et al.
    • Journal Title

      Int.Immunol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Neural crest stem cells and organogenesis.2005

    • Author(s)
      Yamazaki, H., et al.
    • Journal Title

      Progress in Stem Cell Research (Nova Science Publishers) (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enforced expression of PU.1 rescues osteoclastogenesis from embryonic stem cells lacking Tal-1.2005

    • Author(s)
      Tsuneto, M., Tominaga, A., Yamazaki, H., Yoshino, M., Orkin, S.H., Hayashi, S.I.
    • Journal Title

      Stem Cells 23

      Pages: 134-143

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neural crest stem cells and organogenesis.2005

    • Author(s)
      Yamazaki, H., et al.
    • Journal Title

      Trends in Stem Cell Research, Nova Science Publishers (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice.2004

    • Author(s)
      Hayashi, S.I., et al.
    • Journal Title

      Endocrinology 145

      Pages: 2721-2729

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Migration of dendritic cells determines divergent immune responses2004

    • Author(s)
      Yoshino, M., et al.
    • Journal Title

      Recent Research Development in Biophysics and Biochemistry (Research Signpost) 4

      Pages: 29-48

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Contribution of neural crest cells in the tooth development and the possibility of tooth regeneration2004

    • Author(s)
      Yamazaki, H., Hayashi, S.I.
    • Journal Title

      J.Oral.Sci. 46

      Pages: 509-518

    • NAID

      110003166651

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice.2004

    • Author(s)
      Hayashi.S.I., Tsuneto, M., Yamada, T., Nose, M., Yoshino, M., Shultz, L.D., Yamazaki, H.
    • Journal Title

      Endocrinology 145

      Pages: 2721-2729

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteoclast Lineage (Chapter 27).2004

    • Author(s)
      Yamane, T., Okuyama, H., Tsuneto, M., Hemmi, H., Yamazaki, H., Hayashi.S.I.
    • Journal Title

      Handbook of Stem Cells (Eds.R.P.Lanza, et al.)(Academic Press, San Diego, CA.)Embryonic Stem Cells Vol.1

      Pages: 295-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Migration of dendritic cells determines divergent immune responses.2004

    • Author(s)
      Yoshino, M., Yamazaki, H., Hayashi.S.I.
    • Journal Title

      Recent Research Development in Biophysics and Biochemistry (Research Signpost) 4

      Pages: 29-48

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Contribution of neural crest cells in the tooth development and the possibility of tooth regeneration.2004

    • Author(s)
      Yamazaki, H., Hayashi, S.I.
    • Journal Title

      J.Oral.Sci. 46

      Pages: 509-518

    • NAID

      110003166651

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells2003

    • Author(s)
      Yamada, T., et al.
    • Journal Title

      Blood 101

      Pages: 2227-2234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption2003

    • Author(s)
      Yoshino, M., et al.
    • Journal Title

      J.Bone Miner.Res. 18

      Pages: 108-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells2003

    • Author(s)
      Hirano, M., et al.
    • Journal Title

      Dev.Dyn. 228

      Pages: 664-671

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-α2003

    • Author(s)
      Hayashi, S.I., et al.
    • Journal Title

      J.Immunol. 171

      Pages: 5130-5139

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Discrete types of osteoclast precursors can be generated from embryonic stem cells2003

    • Author(s)
      Okuyama, H., et al.
    • Journal Title

      Stem Cells 21

      Pages: 670-680

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Distinct antigen trafficking from skin in the steady and active states.2003

    • Author(s)
      Yoshino, M., et al.
    • Journal Title

      Int.Immunol. 15

      Pages: 773-779

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] In vitro differentiation of mouse ES cells into hematopoietic, endothelial, andosteoblastic cell lineages : A possibility of in vitro organogenesis2003

    • Author(s)
      Tsuneto, M., et al.
    • Journal Title

      Methods Enzymol. 365

      Pages: 98-114

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Tooth development and tooth regeneration using tooth germ, dental pulp cells, neural crest cells and embryonic stem cells2003

    • Author(s)
      Yamazaki, H., et al.
    • Journal Title

      Recent Research Development in Biophysics and Biochemistry. (Research Signpost) 3

      Pages: 907-925

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through atromal cells.2003

    • Author(s)
      Yamada, T., Yamazaki, H., Yamane, T., Yoshino, M., Okuyama, H., Tsuneto, M., Kurino, T, Hayashi, S.I., Sakano, S.
    • Journal Title

      Blood 101

      Pages: 2227-2234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption.2003

    • Author(s)
      Yoshino, M., Yamazaki, H., Yoshida, H., Niida, S., Nishikawa, S.I., Ryoke, K., Kunisada, T., Hayashi, S.I.
    • Journal Title

      J.Bone Miner.Res. 18

      Pages: 108-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells.2003

    • Author(s)
      Hirano, M., Yamamoto, A., Yoshimura, N., Tokunaga, T., Motohashi, T., Ishizaki, K., Yoshida, H., Okazaki, K, Yamazaki, H., Hayashi, S.I., Kunisada, T.
    • Journal Title

      Dev.Dyn. 228

      Pages: 664-671

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-α2003

    • Author(s)
      Hayashi.S.I., Yamada, T., Tsuneto, M., Yamane, T., Takahashi, M., Shultz, L.D., Yamazaki H.
    • Journal Title

      J.Immunol. 171

      Pages: 5130-5139

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Discrete types of osteoclast precursors can be generated from embryonic stem cells.2003

    • Author(s)
      Okuyama, H., Tsuneto, M., Yamane, T., Yamazaki, H., Hayashi, S.I.
    • Journal Title

      Stem Cells 21

      Pages: 670-680

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distinct antigen trafficking from skin in the steady and active states.2003

    • Author(s)
      Yoshino, M., Yamazaki, H., Nakano, H., Kakiuchi, T., Ryoke, K., Kunisada, T., Hayashi, S.I.
    • Journal Title

      Int.Immunol. 15

      Pages: 773-779

    • NAID

      10014341739

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro differentiation of mouse ES cells into hematopoietic, endothelial, and osteoblastic cell lineages : A possibility of in vitro organogenesis.2003

    • Author(s)
      Tsuneto, M., Yamane, T., Okuyama, H., Yamazaki, H., Hayashi, S.I.
    • Journal Title

      Differentiation of Embryonic Stem Cells (Eds.P.M.Wassarman, and G.M.Keller)(Academic Press, San Diego, CA) Methods Enzymol. 365

      Pages: 98-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tooth development and tooth regeneration using tooth germ, dental pulp cells, neural crest cells and embryonic stem cells.2003

    • Author(s)
      Yamazaki, H., Kurino, T., Sakata, E., Yoshino, M., Hayashi.S.I.
    • Journal Title

      Recent Research Development in Biophysics and Biochemistry (Research Signpost) 3

      Pages: 907-925

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation.

    • Author(s)
      Yamazaki, H., Sakata, E., Yamane, T., Yanagisawa, A., Abe, K., Yamamura, K.I., Hayashi, S.I., Kunisada, T.
    • Journal Title

      Int.Immunol. (In press)

    • NAID

      10019359234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neural crest stem cells and organogenesis.

    • Author(s)
      Yamazaki, H., Yoshino, M., Hayashi, S.I.
    • Journal Title

      Progress in Stem Cell Research (Ed.F.Columbus)(Nova Science Publishers, Inc., Hauppauge, NY.) (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Osteoclast Lineage (Chapter 27) (pp295-303, Handbook of Stem Cells, Vol.1, Embryonic Stem Cells)2004

    • Author(s)
      Yamane, T., et al.
    • Total Pages
      806
    • Publisher
      Academic Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Osteoclast Lineage (Chapter 27) pp295-303, Handbook of Stem Cells, Vol.1, Embryonic Stem Cells".2004

    • Author(s)
      Yamane, T., et al.
    • Total Pages
      806
    • Publisher
      Academic Press
    • Related Report
      2004 Annual Research Report
  • [Publications] Yamada, T., et al.: "Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells"Blood. 101. 2227-2234 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino, M., et al.: "Reduction of osteoclasts in the critical embryonic period is essential for inhibition of mouse tooth eruption"J.Bone Miner.Res.. 18. 108-116 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino, M., et al.: "Distinct antigen trafficking from skin in the steady and active states"Int.Immunol.. 15. 773-779 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okuyama, H., et al.: "Discrete types of osteoclast precursors can be generated from embryonic stem cells"Stem Cells. 21. 670-680 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi, S.I., et al.: "Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-α"J.Immunol.. 171. 5130-5139 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirano, M., et al.: "Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells"Dev.Dyn.. 228. 664-671 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuneto, M., et al.: "In vitro differentiation of mouse ES cells into hematopoietic, endothelial, and osteoblastic cell lineages : A possibility of in vitro organogenesis"Methods Enzymol.. 365. 98-114 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamazaki, H., et al.: "Tooth development and tooth regeneration using tooth germ, dental pulp cells, neural crest cells and embryonic stem cells"Recent Research Development in Biophysics and Biochemistry (Research Signpost). 3. 907-925 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi, S.I., et al.: "Lipopolysaccharide-induced osteoclastogenesis in SHP-1-deficient viable motheaten mice"Endocrinology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamane, T., et al.: "Osteoclast Lineage. In"Handbook of Embryonic Stem Cells""Academic Press(in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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