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2002 Fiscal Year Final Research Report Summary

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
Keywordsapoptosis / neuron / differentiation / mitochondria / regeneration
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

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2004-04-14  

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