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Regulation of lineage commitment of hematopoietic stem cells by the stromal cells

Research Project

Project/Area Number 07458187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

OBINATA Masuo  Institute of Development, Aging and Cancer, Tohoku University Professor, 加齢医学研究所, 教授 (10099971)

Co-Investigator(Kenkyū-buntansha) YANAI Nobuaki  Institute of Development, Aging and Cancer, Tohoku University Assistant professo, 加齢医学研究所, 助手 (80200525)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordshematopoietic stem cells / commitment / c-Kit / SCF / myelopoiesis / lymphopoiesis
Research Abstract

To know the regulatory mechanism of lineage commitment of hematopoietic stem cells by the stromal cells in bone marrow, the sorted stem cells were cocultured on 2 established stromal cells. TBR59 stromal cells support myelopoisis and lymphopoiesis of the sorted stem cells. Another cell line, TBR31-1 was shown to specifically induce B-lymphopoiesis. In both cocultures, the commitment of differentiation of the stem cells toward myeloid and lymphoid was observed without exogenously added soluble factors. Finally we obtained two immortalized stem-like cell lines depending on the stromal cells. One is B-lymphoid stem-like cell line and the other is stem cell-like cell lines with surface markers and both cell lines can be differentiated.
We examined molecules involved in the interaction between the stromal and stem cells and found that c-Kit and its ligand, SCF,VLA-4, an integrin, or VCAM-1, a ligand for VLA-4, are necessary factors. To know other factors involved in the stromal cells, we made monoclonal antibodies to each stromal cell line and obtained specific monoclonal antibodies to one type of the stromal cells. Then, the expression cDNA library made from the two cell lines was used for screening of the antigenic molecules recognized by these antibodies.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Nemoto,Y.: "Regulatory function of delta/YY-1 on the locus control region(LCR)-like sequence of mouse glycophorin gene in erythroleukemia cells." J.Biol.Chem.271. 13542-13548 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Furuchi,T.: "Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spematogonia." Development. 122. 1703-1709 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanai,N.: "v-Src interferes with the in vitro erythropoietic stimulatory abiliy of the spleen strowal cells througy repression of VCAM-1 and SCF." Exp.Hematol.24. 883-887 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mataga,N.: "Establishament of a novel chondrocyte-like cell line derired from transgenic mice harboring temperature sensitive Simian Virus 40large T-antigen gone." J.Bone and Mineral Res.11. 1646-1654 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kodaira,K.: "Overexpression of c-Myc induces apoptosis at prophase of rat primary spermacytes." Mol.Reprod.Dev.45. 403-410 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanagisawa,M.: "Anovel serine/threonine kinase gene,Gek 1,is expressed in meiotic testicalar germ cells and primodial germ cells." Mol.Reprod.Dev.45. 411-420 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obinata.M.: "challenges of Modern Medicine,Vol.10, Differentiation Therapy" ed by S.Waxman,Ares-Sereno Symposia Publications,Rome.Italy, 5 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obinata.M.: "challenges of Modern Medicine,Vol.10,Differentiation Therapy" ed by S.Waxman,Ares-Sereno Symposia Publications,Rome,Italy, 6 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nemoto, Y., Terajima, M., Shoji, W., and Obinata, M.: "Regulatory function of delta/YY-1 on the locus control region (LCR)-like sequence of mouse glycophorin gene in erythroleukemia cells." J.Biol.Chem.271. 13542-13548 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Furuchi T., Masuko, K., Nishimune Y., Obinata, M.and Matsui Y.: "Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia" Development. 122. 1703-1709 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanai, N., Shimizu, A., Koguma, M.and Obinata, M.: "v-Src interferes with the in vitro erythropoietic stimulatory ability of the spleen stromal cells through repression of VCAM-1 (Vascular Cell Adhesion Molecule-1) and SCF (Stem Cell Factor)" Exp.Hematol.24. 883-887 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mataga, N., Tamura, M., Yanai, N., Shimomura, T., Kimata, K., Obinata, M.and Noda, M.: "Establishment of a novel chondrocyte-like cell line derived from transgenic mice harboring temperature sensitive Simian Virus 40 large T-antigen gene." J.Bone and Mineral Res.11. 1646-1654 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kodaira, K., Takahashi, R., Hirabayashi, M., Suzuki, T., Obinata, M.and Ueda, M.: "Overexpression of c-Myc induces apoptosis at prophase of rat primary spermatocytes" Mol.Reprod.Dev.45. 403-410 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanagisawa, M., Mukouyama, Y., Watanabe, T., Obinata, M., and Matsui, Y.: "A novel serine/threonine kinase gene, Gek1, is expressed in meiotic testicular germ cells and primodial germ cells" Mol.Reprod.Dev.45. 411-420 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nemoto, Y.: "Regulatory function of delta/YY-1 on the locus control region (LCR) -like sequence of mouse glycophorin gene in erythroleukemia cells." J. Biol. Chem.271. 13542-13548 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Furuchi, T.: "Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bel-2 in spermatogonia." Development. 122. 1703-1709 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yanai, N.: "V-Src interferes with the in vitro erythropietic stimulatory ability of the spker stroual cells through repression of VCAM-1 ad SCF." Exp. Hematol.24. 883-887 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mataga, N.: "Establishment of a novel chondrocyte-like cell line derived from tromsgenic mice harboring temperature sensitive Simion Virus 40 large T-antigen gene." J. Bone and Mineral Res.11. 1464-1654 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kodaira, K.: "Overexpression of c-Myc induces apoptosis at prophase of rat primary spermacytes." Mol. Reprod. Dev.45. 403-410 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yanagisawa, M.: "Anovel serine/threonine kinase gene, Gek 1, is expressed in meiotic testicular germ cells and primodial germ cells." Mol. Reprod. Dev.45. 411-420 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Obinata, M.: "Challenges of Modern Medicine, Vol. 10, Differentiation Therapy" ed by S. Waxman, Ares-Sereno Symposia Publications, Rome. Italy, 5 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Obinata, M.: "Challenges of Modern Medicine, Vol. 10, Defferentiation Therapy" ed by S. Waxman, Ares-Sereno Symposia Publications, Rome, Italy, 6 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shoji,W.: "MIDA1,a protein associated with Id,regulates cell growth." J.Biol.Chem.270. 24818-24825 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kameoka,J.-I.: "Bone marrow stromal cells selectively stimulate the rapid expansion of lineage-restricted myeloid progenitors." J.Cell.Physiol.164. 55-64 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okuyama,R.: "Bone marrow stromal cells induce myeloid and lymphoid development of the sorted hematopoietic stem cells in vitro." Blood. 86. 2590-2597 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okuyama,R.: "Differentiation capacity towards mesenchymal cell lineages of bone marrow stromal cells established from temperature-sensitive SV40 T-antigen Transgsnic mouse." Exp.Cell Res.218. 424-429 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taher,A.: "Properties of incompletely immortalized cell lines generated from the line established from temperature-sensitive SV40 T-antigen Transgenic mice." Exp.Cell Res.219. 332-338 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nemoto,Y.: "Regulatory function of delta/YY-1 on the locus control region(LCR)-like sequence of mouse glycophorin gene in erythroleukemia cells." J.Biol.Chem.(in Press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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