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1999 Fiscal Year Final Research Report Summary

Practical development of a novel method for hematopoietic stem cell expansion

Research Project

Project/Area Number 09357010
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

HIRAI Hisamaru  Internal Medicine, University of Tokyo Hospital, Associate Professor, 医学部・附属病院, 助教授 (90181130)

Co-Investigator(Kenkyū-buntansha) HONDA Hiroaki  Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (40245064)
CHIBA Shigeru  Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60212049)
MITANI Kinuko  Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (50251244)
OGAWA Seishi  Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60292900)
SASAKI Ko  Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60282638)
Project Period (FY) 1997 – 1999
KeywordsNotch / DSL domain / Jagged1 / differentiation / active Notch1 / transcription factor / GATA-2
Research Abstract

The Delta/Serrate/LAG-2 (DSL) domain-containing proteins are considered to be ligands for Notch receptors. However, the physical interaction between DSL proteins and Notch receptors is poorly understood. We found that mJagged1 physically bound to mouse Notch2 (mNotch2) on the cell surface and to a purified extracellular portion of mNotch2, respectively, in a CaィイD22+-ィエD2dependent manner. Deletion mutant analyses showed that the DSL Domain of mJagged1 is a minimal binding unit and is indispensable for binding to mNotch2. The solid-phase binding assay showed that Jagged1 binds to Notch1 and Notch3 in addition to Notch2, suggesting that mJagged1 is a ligand for multiple Notch receptors. We further analyzed the expression levels of transcription factors, C/EBP α, C/EBPε, PU.1, AML1b, c-myb, and GATA-2 as myeloid-specific transcription factors, and SCL, GATA-1, GATA-2, NF-E2 (p45), MafK (p18), EKLF, and c-myb as erythroid-specific transcription factors, before and after stimulation for differentiation of the wild-type and aNotch1-expressing 32D myeloid cells and F5-5 erythroid cells, respectively. As a result, the expression levels of those transcription factors except GATA-2 showed the same pattern in the wild-type and aNotch1-expressing cells, whereas the expression level of GATA-2 was found unchanged after stimulation for differentiation in the aNotch1-expressing 32D cells but decreased in the wild-type cells, suggesting inhibition of differentiation by aNotch1 is mediated through GATA-2.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Takahashi T: "Apotential molecular approach to ex vivo hematopoietic expansion with recombinant EFFR -expressing adenvovirus vector."Blood. 91. 4509-4515 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurokawa M: "The oncoprotein Evi-1 represses TGFb signalling by inhibiting Smad3"Nature. 394. 92-96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Honda H: "Cardiovascular anomaly, impaired actin bundling and resistance to Src induced transformation in mice lacking p130Cas."Nature Genet.. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Honda H: "Expression of E2A-HLF chimeric protein induced T-cell apoptosis, B-cell matruation arrest and development of acute lymphoblalstic leukemia"Blood. 93. 2780-2790 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu K: "Mouse Jagged1 physically interacts with Notch2 and other Notch receptors: asssessment by quantitative methods"J. Biol. Chem.. 274. 32961-32969 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamoto T: "CIZ: a zine finger protein that interacts with p130cas and activates the expression of matrix metalloproteinases."Mol. Cell. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahasi T, Yamada K, Tanaka T, Kumano K, Kurokawa M, Takahashi T, Hirano N, Honda H, Chiba S, Tsuji K, Yazaki Y, Nakahata T, Hirai H.]: "A potential molecular approach to ex vivo hematopoietic expansion with recombinant EGFR-expressing adenovirus vector."Blood. 91. 4509-4515 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurokawa M, Mitani K, Irie K, Matsuyama T, Takahashi T, Chiba S, Yazaki Y, Matsumoto K, Hirai H.: "The oncoprotein Evi-represses TGFβ signalling by inhibiting Smad3."Nature. 394. 92-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Honda H, Oda, H, Nakamoto T, Honda Z, Sakai R, Suzuki T, Saito T, Nakamura K, Nakao K, Ishikawa T, Katsuki M, Yazaki Y, Hirai H.: "Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas."Nature Genet.. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Honda H, Inaba T, Suzuki T, Oda H, Ebihara Y, Tsuiji K, Nakahata T, Ishikawa T, Yazaki Y, Hirai H.: "Expression of E2A-HLF chimeric protein induced T-cell apoptosis, B-cell maturation arrest and development of acute lymphoblastic leukemia."Blood. 93. 2780-2790 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H.: "Mouse Jagged1 physically interacts with Notch2 and other Notch receptors : assessment by quantitative methods."J. Biol. Chem.. 274. 32961-32969 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H.: "CIZ : a zinc finger protein that interacts with p130cas and activates the expression of matrix metalloproteinases."Mol. Cell. Biol.. (In press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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