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2004 Fiscal Year Final Research Report Summary

Production of cells that constitute microenvironment of cancer.

Research Project

Project/Area Number 12219209
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe Institute of Physical and Chemical Research (2003-2004)
Kyoto University (2000-2002)

Principal Investigator

NISHIKAWA Shun-Ichi  The institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Group Director, 幹細胞研究グループ, グループディレクター (60127115)

Co-Investigator(Kenkyū-buntansha) ERA Takumi  The Institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (00273706)
OSAWA Masatake  The lnstitute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (10344029)
UEMURA Akiyoshi  The Institute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (30373278)
TOGAWA Atsushi  The lnstitute of Physical and Chemical Research, Laboratory for Stem Cell Biology, Research Scientist, 幹細胞研究グループ, 研究員 (30359799)
Project Period (FY) 2000 – 2004
KeywordsES cell / endothelial cell / stem cell / mesoderm / melanocyte / bulge region / mesenchymal stem cell / DNA microarray
Research Abstract

1) We established a method to induce vascular components from ES cells that enables cellular analysis of normal endothelial and mural cells. Using this experimental system, we determine the role of Fik1, Fit1, and Flt4 in endothelial cells. Moreover, we have identified a culture condition to induce endothelial cells from human ES cells.
2) We established a method to manipulate angiogenesis in the neonatal retina by intraocular injection of various reagents. Using this system, we have identified LIF and Tlx as molecules regulating astrocyte-endothelial intereactions, and PDGFRβ, Ang1, and Plexin D1 as molecules involved in interaction between endothelial cells and mural cells.
3) Using a culture system to induce ES cell differentiation to hematopoietic stem cells, we identify the stage when SCL, Runx1 and GATA1 are involved. While we succeeded to determine a defined culture condition to induce endothelial and hematopoietic cells from ES cells, we could not attain the goal to induce the de … More finitive hematopoietic stem cells from ES cells.
4) We have established a defined condition that allows selective induction of the definitive endoderm and demonstrated presence of bipotent mesendoderm that can give rise to both definitive endoderm and mesoderm.
5) Taking advantage of a data base that contains DNA microarray data of varying intermediate stages appearing in ES cell differentiation culture (this data base is a project of Kobe City), we tested a new method to isolate novel genes that are involved in various process of cell specification during embryogenesis. We have identified three novel molecules and proved that they are indeed play an essential role in embryogenesis.
6) We determined that the stem cell compartment of melanocyte system locates in the bulge-region of hair follicles. Those melanocyte stem cells are picked up individually to make a stem cell specific library From the gene expression profile in this library, we found that the stem cell compartment is characterized by its low expression of house keeping genes. We also found that the stem cell expresses a high level of 1) Wnt inhibitors, 2) Notch/Hes1, and 3) molecules that may potentially suppress basic transcriptional machinery. Among those characteristics, we investigated the role of Notch signaling in melanocyte, and demonstrated that Notch/Hes1 signaling is essential for melanocyte development and maintenance of the stem cell compartment.
7) We demonstrated that a part of mesenchymal stem cells are derived from neuroepithelial cells. Less

  • Research Products

    (16 results)

All 2005 2004 2003 2002 2001 2000 Other

All Journal Article (14 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] A high level of endothelial cell-specifie gene expression by a combination of 5' flanking region and 5' half of the first intron of VE-cadherin gene.2005

    • Author(s)
      Hisatsune H, Matsumura K, Ogawa M, Uemura A, Kondo N, Yamashita JK, Katsuta H, Nishikawa S, Chiba T, Nishikawa SI
    • Journal Title

      Blood (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neural crest and the origin of ectomesenchyme : Neural fold heterogeneity suggests an alternative hypothesis.2004

    • Author(s)
      Weston JA, Yoshida H, Robinson V, Nishikawa S, Fraser ST, Nishikawa S.
    • Journal Title

      Dev Dyn 229

      Pages: 118-130

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells.2003

    • Author(s)
      Hiroshima M, Ogawa M, Nishikawa S, Matsumura K, Kawasaki K, Shibuya M, Nishikawa SI
    • Journal Title

      Blood 101

      Pages: 2261-2267

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells.2003

    • Author(s)
      Hirashima M, Ogawa M, Nishikawa S, Matsumura K, Kawasaki K, Shibuya M, Nishikawa SI.
    • Journal Title

      Blood. 101

      Pages: 2261-2267

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dominant role of the niche in melanocyte stem-cell fate determination.2002

    • Author(s)
      Nishimura EK, Jordan SA, Oshima H, Ybshida H, Osawa M, Moriyama M, Jackson IJ, Barrandon Y, Miyachi Y, Nishikawa S
    • Journal Title

      Nature 416

      Pages: 854-860

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches.2002

    • Author(s)
      Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, Ware CF, Togawa A, Nishikawa S, Nishikawa SI
    • Journal Title

      Immunity 17

      Pages: 823-833

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dominant role of the niche in melanocyte stem-cell fate determination.2002

    • Author(s)
      Nishimura EK, Jordan SA, Oshima H, Yoshida H, Osawa M, Moriyama M, Jackson IJ, Barrandon Y, Miyachi Y, Nishikawa S.
    • Journal Title

      Nature. 416

      Pages: 854-860

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells.2002

    • Author(s)
      Uemura A, Ogawa M, Hirashima M, Fujiwara T, Koyama S, Takagi H, Honda Y, Wiegand SJ, Yancopoulos GD, Nishikawa S.
    • Journal Title

      J Clin Invest. 110

      Pages: 1619-1628

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches.2002

    • Author(s)
      Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, Ware CF, Togawa A, Nishikawa S, Nishikawa SI.
    • Journal Title

      Immunity. 17

      Pages: 823-833

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer' s patch organogenesis.2001

    • Author(s)
      Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, J Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa SI
    • Journal Title

      J. Exp. Med. 195

      Pages: 621-630

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis.2001

    • Author(s)
      Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa SI.
    • Journal Title

      J Exp Med. 193

      Pages: 621-630

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Flk1-positive cells der ived from embryonic stem cells serve as vascular progenitors.2000

    • Author(s)
      Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M, Nakao K, Nishikawa SI
    • Journal Title

      Nature 408

      Pages: 92-96

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors.2000

    • Author(s)
      Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M, Nakao K, Nishikawa SI
    • Journal Title

      Nature. 408

      Pages: 92-96

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A high level of endothelial cell-specific gene expression by a combination of 5' flanking region and 5' half of the first intron of VE-cadherin gene.

    • Author(s)
      Hisatsune H, Matsumura K, Ogawa M, Uemura A, Kondo N, Yamashita JK, Katsuta H, Nishikawa S, Chiba T, Nishikawa SI.
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 脂肪前駆細胞2004

    • Inventor(s)
      江良拓実, 西川伸一
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      PCT/JP2004/007735号
    • Filing Date
      2004-05-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 内胚葉系幹細胞の調整2004

    • Inventor(s)
      江良拓実, 西川伸一
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      CT/JP2004/007227号
    • Filing Date
      2004-05-20
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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