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造血幹細胞と血管幹細胞における遺伝子発現の系統的解析

Research Project

Project/Area Number 14657247
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKeio University

Principal Investigator

須田 年生  慶應義塾大学, 医学部, 教授 (60118453)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords造血幹細胞 / 血管前駆細胞 / 遺伝子発現 / Side Population / Main Population / p21 / 細胞周期遺伝子 / Sir2
Research Abstract

本研究では、造血幹細胞と血管前駆細胞の遺伝子発現をDNA arrayを用いて、系統的に解析しその異同を明らかにすることを目的とした。ここでは、未分化細胞集団に限定し、しかもin vitro培養系において、高率に純化された細胞群を対照として用いる。
今年度は以下のことを明らかにした。
1)マウス骨髄幹細胞(c-Kit陽性Sca-1陽惟Lin陰性細胞:KSL細胞)は、蛍光色素排出率の高いSide Population (SP)と低いMain Population (MP)に分かれることが明らかとなった。SPは、胎仔肝や新生仔期骨髄には認められず、生後4週頃より検出できる。我々は、SP細胞の70-80%がTIE2陽性細胞であることを見いだした。骨髄組織の免疫染色により、幹細胞は骨芽細胞の近く、あるいは、それに接して存在することを明らかにした。さらに、アンジオポエチン-1は、TIE2受容体を介して、幹細胞がニッチと接着するのを誘導することを示した(Arai F, Hirao A et al, Cell, in revise)。
2)マウスES細胞から、造血細胞と血管内皮細胞の分化誘導をはかり、遺伝子の発現を解析した。造血幹細胞には、TIE2, GATA-2, Evi-1, nanogなどの分子が発現していることを確認した(Hamaguchi I, et al, in preparation)。しかしながら、血管幹細胞特異的遺伝子を同定することはできなかった。

Report

(2 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Oike Y, et al.: "Angiopoietin-related growth factor (AGF) promotes angiogenesis"Blood. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsunematsu R, et al.: "Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development."J.Biol.Chem.. DEC 12(Epub ahead of print). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamada K, et al.: "Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells."Arterioscler.Thromb.Vasc.Biol.. 23. 190-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyamoto T, et al.: "Differentiation and function of osteoclasts."The Keio Journal of Medicine. 52. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada Y, et al.: "Neuropilin-1 on hematopoietic cells as a source of vascular development."Blood. 101. 1801-1809 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohbo K, et al.: "Identification and characterization of stem cells in prepubertal spermatogenesis in mice."Dev.Biol.. 258. 209-225 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oike Y, et al.: "Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling and regeneration."Proc.Natl.Acad.Sci.USA. 100. 9494-9499 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Li Z, et al.: "Defective smooth muscle development in qkI deficient mice."Dev.Growth Differ.. 45. 449-462 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito Y, et al.: "Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4."Cancer Res.. 63. 6651-6657 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maekawa H, et al.: "Ephrin-B2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature."Arterioscler.Thromb.Vasc.Biol. 23. 190-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nasaka K et al.: "Increased RANK ligand expression on adult T-cell leukemia cells is the critical factor of hyper-calcemia"Blood. 99. 634-640 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oike Y et al.: "Regulation of vasculogenesis and angiogenesis by Eph/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells"Blood. 100. 1326-1333 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arai F et al.: "Mesenchymal stem cells in perichondrium express activated cell adhesion molecule and participate in bone formation"J. Exp. Med. 195. 1449-1563 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suenobu S et al.: "A role of EphB4 receptor and its ligand, ephrin-B2 in erythropoiesis"Biochem Biophys Res Comm. 293. 1124-1131 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamada K et al.: "Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells"Arterioscler Thromb Vasc Biol. 23(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohbo K et al.: "Identification and characterization of stem cells in pre-pubertal spermatogenesis"Dev. Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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