Mechanisms of Development and Regeneration of Mammalian Central Nervous System
| Project/Area Number |
13480267
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Keio University |
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Principal Investigator |
SHIMAZAKI Takuya Keio University, School of Medicine, Instructor, 医学部, 助手 (00324749)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | ES cells / Neural progenitor cell / Stem cell / Cholinergic neuron / Motoneuron / GABAergic neuron / Dopaminergic neuron / Retinoic Acid / 時系列特異的 / DNAマイクロアレイ / 遺伝子発現プロファイリング / neurosphere / 霊長類 / Embryoid Body (EB) / 神経幹細胞 / 神経前駆細胞 / Phox2B / Embryoid Body(EB) / HB9 / noggin / GABAニューロン |
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| Research Abstract |
Firstly, we have developed a system to obtain neural progenitor cells including stem cells from mouse ES cells through the induction of differentiation by embryoid body (EB) formation and a subsequent floating culture called neurosphere culture which selectively amplifies neural stem/progenitor cells (NSPCs). These progenitor cells differentiate into virtually only neurons that are mainly cholinergic or GABAergic. Then, transplantation of these ES-derived neural progenitors into hippocampus of mice that had memory deficit by cholinergic lesion in their septum resulted amelioration of the deficit and differentiation of the progenitors into neurons including cholinergic neurons.
On the other hand, we have succeeded to purify EGFP expressing neural stem cells and dopaminergic neurons derived from genetically modified mouse ES cells differentiated on the PA-6 stromal cell feeder layer by FACS. Transplantation of these FACS purified dopaminergic neurons into striatum of Parkinsonian model rats resulted partial amelioration of the symptoms.
We also have developed a system to derivate NSPCs which can efficiently generate somatic motoneurons expressing HB9 transcription factor and hindbrain visceral motoneurons expressing PhoxB transcription factor from mouse ES cells through EB formation. Moreover, we have found that generation of various types of motoneurons from ES cells can be controlled by the exposure EBs to various concentration retinoic acid.
Finally, we have successfully developed a system to derivate NSPCs and neurons from crab-eating monkey and human ES cells by applying the systems developed for mouse ES cells with slight modifications in the culture conditions and periods.
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Report
(5 results)
Research Products
(37 results)
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[Journal Article] Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells.2004
Author(s)
Yoshizaki T, Inaji M., Kouike H., Shimazaki T, Sawamoto K, Ando K, Date I, Kobayashi K, Suhara T, Uchiyama Y, Okano H.
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Journal Title
Neurosci Lett 363
Pages: 33-37
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils.2004
Author(s)
shibashi S, Sakaguchi M, Kuroiwa T, Yamasaki M, Kanemura Y, Shizuko I, Shimazaki T, Onodera M, Okano H, Mizusawa H.
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Journal Title
J Neurosci Res 78
Pages: 215-223
Related Report
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[Journal Article] Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells.2004
Author(s)
Yoshizaki T, Inaji M, Kouike H, Shimazaki T, Sawamoto K, Ando K, Date I, Kobayashi K, Suhara T, Uchiyama Y, Okano H
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Journal Title
Neurosci Lett 363
Pages: 33-37
Related Report
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[Journal Article] Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryos.2003
Author(s)
Kokuzawa J, Yoshimura S, Kitajima H, Shinoda J, Kaku Y, Iwama T, Morishita R, Shimazaki T, Okano H, Kunisada T, Sakai N.
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Journal Title
Mol Cell Neurosci 24
Pages: 190-197
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Kokuzawa J., Yoshimura S., Kitajima H., Shinoda J., Kaku Y, Iwama T., Morishita R., Shimazaki T., Okano H., Kunisada T., Sakai N.: "Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryos."Mol Cell Neurosci. 24. 190-197 (2003)
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[Publications] Kohyama, J., Abe, H., Shimazaki, T., Koizumi, A., Nakashima, K., Gojo, S., Taga, T., Okano, H., Hata, J., Umezawa, A.: "Brain from bone : efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent"Differentiation. 68. 235-244 (2001)
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