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Study of differentiation of apoptosis-resistant nerve stem cells and their application to neuroregeneration

Research Project

Project/Area Number 13558093
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Nerve anatomy/Neuropathology
Research InstitutionKyushu University

Principal Investigator

YOSHIDA Hiroki  Kyushu University, Med. Inst. Bioreg. Associate Professor, 生体防御医学研究所, 助教授 (40260715)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Kinichi  KumamotoUniversity, Inst. Mol. Embryol. Genetics Associate Prof., 発生医学研究センター, 助教授 (80302892)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2001: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordsapoptosis / neuron / differentiation / mitochondria / regeneration / 神経幹細胞 / Apaf1
Research Abstract

First we examined the development of neurons in Apaf1- and Bc1-XL-doubly knockout embryos. In the doubly-knockout mice, there was accumulation of neurons just as in Apaf1-single knockout embryos. However, differentiation of nerve stem cells into mature neurons was normal in both Apaf1-single and doubly knockout mice. Next we demonstrated BMP2drives the differentiation f nerve stem cells into astrocytes. Practically, BMP2 suppresses the differentiation of stem cells into neurons by the induction of inhibitory HLH factors and the resultant suppression of bHLH transcription factors that favor nerve differentiation. In regeneration of therapies of nerve/spine, it is a serious problem that transplanted stem cells tend to differentiate into astorocytes. Another problem will be the poor viability of transplanted stem cells in the host. Since Apaf1-deficient stem cells are resistant to various apoptotic stimuli while showing normal differentiation into neurons, our results may shed light to the development of novel neuroregenerative therapies by driving the differentiation of apoptosis-resistant stem cells arbitrarily into neurons

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Yoshida, et al.: "Differential requirement for Apaf1 and Bcl-XL in the regulation of programmed cell death during development"Cell death and differentiation. 9. 1273-1276 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Z.Guo, et al.: "Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease-activating factor-1 dependent and independent apoptotic pathways during embryogenesis"Cancer research. 61. 8395-8400 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Joza, et al.: "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death"Nature. 410. 549-554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Nakashima, T.Taga: "Mechanisms underlying cytokine-mediated cell-fate regulation in the nervous system"Molecular Neurobiology. 25. 233-244 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Nakashima, et al.: "BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis"Proc. Natl. Sci. USA.. 98. 5868-5873 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Takizawa, et al.: "DNA methylation is a critical -cell-intrinsic determinant of astrocyte differentiation in the fetal brain"Dev. Cell. 1. 749-758 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Yoshida, et al.: "Differential requirement for Apaf1 and Bc1-XL in the regulation of programmed cell death during development"Cell death and differentiation. 9. 1273-1276 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Z. Guo, et al.: "Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease activating factor-1 dependent and independent apoptotic pathways during embryogenesis"Cancer research. 61. 8395-8400 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Joza, et al.: "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death"Nature. 410. 549-554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Nakashima, and T. Taga: "Mechanisms underlying cytokine-mediated cell-fate regulation in the nervous system"Molesular neurobiology. 25. 233-244 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Nakashima, et al.: "BMP2-raediaed alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis"Proc. Nat1. Sci. USA.. 98. 5868-5873 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Takizawa, et al.: "DNA methylation is a ritical cell-intrinsic determinant of astrocyte differentiation in the fetal brain"Dev.Cell. 1. 749-758 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida, H. 他: "Differential requirement for Apaf1 and Bcl-X(L) in the regulation of programmed cell death during development"Cell Death Differ. 9・11. 1273-1276 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayanagi, H. 他: "Induction and Activation of the Transcription Factor NFATc1 (NFAT2) Integrate RANKL Signaling in Terminal Differentiation of Osteoclasts"Dev Cell. 3・6. 889-901 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inagaki-Ohara, K. 他: "Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves both caspase-3-dependent and-independent pathways"Dig Dis Sci. 47・12. 2823-2830 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakashima, K., 他: "BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis"Proc. Natl. Acad. Sci. USA.. 98・10. 5868-5873 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takizawa, T., 他: "DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain"Dev Cell. 1・6. 749-758 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yanagisawa, M., 他: "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7"Genes Cells. 6・12. 1091-1099 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yanagisawa M他: "Fate alteration of neuroepithelial cells from neurogenesis to astrocytogenesis by bone morphogenetic proteins"Neurosci Res. 41(4). 391-396 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takizawa T他: "DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain"Dev Cell. 1(6). 749-758 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanagisawa M他: "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7"Genes Cells. 6(12). 1091-1099 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ochiai W他: "Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3"Cytokine. 14(5). 264-271 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakashima K他: "BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis"Proc Natl Acad Sci USA. 98(10). 5868-5873 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Guo Z他: "Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease-activating factor-1 dependent and independent apoptotic pathways during embryogenesis"Cancer Res. 61(23). 8395-8400 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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