The functional analysis of Sox-6 in neural stem cells for potential application in regenerational medicine

• Project/Area Number: 18500299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: OHTA Shigeki Keio University, School of Medicine, Instructor (20365406)
• Co-Investigator(Kenkyū-buntansha): TODA Msahiro Keio University, School of Medicine, Assistant Professor (20217508)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: Sox6 / Neural Stem Cell / Regenerational medicine / Sox6

Research Abstract

The detailed function of Sox6 in the CNS including neural stem/progenitor cells (NSPCs) has been unclear. In this study, we analyzed the expression of Sox6 in the mouse developing brain and the function in NSPCs. By immunohistochemical analysis, we found that Sox6 was expressed in the ventricular zone of mouse telencephalon at 14.5 dpc, co-localizing with NSPCs's markers, nestin and Sox2. The expression of Sox6 in undifferentiated neurospheres also showed the co-localization with nestin, suggesting that Sox6 may play some roles in NSPCs. To evaluate the function of Sox6 in NSPCs, we performed a neurosphere forming assay in vitro. Over-expression of Sox6 using retrovirus vector in neurospheres caused an increase in the number of secondary neurospheres without changing the proliferation ability as determined by BrdU incorporation assay. Retrovirally over-expressed Sox6 also increased the expression of Hes-1, Bcl-2 and phosphorylated-Akt in the neurospheres. These results suggest that Sox6 is expressed in NSPCs in the developing CNS and involved in the maintenance and/or survival of NSPCs and may contribute to the development of neural degenerative disease treatments based on the activation of endogenous NSPCs.

Research Products

• [Journal Article] Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells following IL-12 administration (2008)
  • Author(s): Yaguchi M, Ohta S, Toyama Y, Kawakami Y, and Toda M
  • Journal Title: J Neurosci Res (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells following IL-12 administration (2008)
  • Author(s): Yaguchi, M., Ohta, S., Toyama, Y., Kawakami, Y., Toda, M
  • Journal Title: J Neurosci Res (In Press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells following IL-12 administration (2008)
  • Author(s): Yaguchi M, Ohta S, Toyama Y, Kawakami Y, Toda M
  • Journal Title: J Neurosci Res
  • Peer Reviewed
• [Journal Article] Preferential expression and frequent IgG responses of a tumor antigen,SOX5, in glioma patients (2007)
  • Author(s): Ueda R, Yoshida K, Kawase T, Kawakami Y, Toda M
  • Journal Title: Int J Cancer 120・8 Pages: 1704-1711
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Isolation and characterization of dendritic cells from common marmosets for preclinical cell therapy studies (2007)
  • Author(s): Ohta S, Ueda Y, Yaguchi M, Matsuzaki Y, Nakamura M, Toyama Y, Tanioka Y, Tamaoki N, Nomura T, Okano H, Kawakami Y, Toda M
  • Journal Title: Immunology Nov.14(Epub ahead of print)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Identification of a neuron-specific human gene,KIAA1110,that is a guanine nucleotide exchange factor for ARF1 (2007)
  • Author(s): Hattori Y, Ohta S, Hamada K, Yamada-Okabe H, Kanemura Y, Matsuzaki Y, Okano H, Kawakami Y, Toda M
  • Journal Title: Biochem Biophys Res Commun 364・4 Pages: 737-742
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients (2007)
  • Author(s): Ueda, R., Yoshida, K., Kawase, T., Kawakami, Y., Toda, M
  • Journal Title: Int, J Cancer 120(8) Pages: 1704-1711
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isolation and characterization of dendritic cells from common marmosets for preclinical cell therapy studies (2007)
  • Author(s): Ohta, S., Ueda, Y., Yaguchi, M., Matsuzaki, Y., Nakamura, M., Toyama, Y., Tanioka, Y., Tamaoki, N., Nomura, T., Okano, H., Kawakami, Y., Toda, M
  • Journal Title: Immunology 14
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of a neuron-specific human gene, KIAA1110, that is a guanine nucleotide exchange factor for ARF1 (2007)
  • Author(s): Hattori, Y., Ohta, S., Hamada, K., Yamada-Okabe, H., Kanemura, Y., Matsuzaki, Y., Okano, H., Kawakami, Y., Toda, M
  • Journal Title: Biochem Biophys Res Commun 364(6) Pages: 737-742
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Preferential expression and frequent IgG responses of a tumor antigen,SOX5,in glioma patients (2007)
  • Author(s): Ueda R, Yoshida K, Kawase T, Kawakami Y, Toda M
  • Journal Title: Int J Cancer 120・8 Pages: 1704-1711
  • Peer Reviewed
• [Journal Article] Isolation and characterization of dendritic cells from commonmarmosets for preclinical cell therapy studies (2007)
  • Author(s): Ohta S, Ueda Y, Yaguchi M, Matsuzaki Y, Nakamura M, Toyama Y, Tanioka Y, Tamaoki N, Nomura T, Okano H, Kawakami Y, Toda M
  • Journal Title: Immunology Nov.14;([Epub ahead of print])
  • Peer Reviewed
• [Journal Article] Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients (2007)
  • Author(s): Ueda R, Yoshida K, Kawase T, Kawakami Y, Toda M
  • Journal Title: Int J Cancer 120 Pages: 1704-1711
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide regulates forebrain neural stem cells and neurogenesis in vitro and in vivo (2006)
  • Author(s): Ohta S, Gregg C, Weiss S
  • Journal Title: J Neurosci Res 84(6) Pages: 177-86
• [Journal Article] Intracarotid injection of granulocyte-macrophage colony stimulating factor induces neuroprotection in a rat transient middle cerebral artery occlusion model (2006)
  • Author(s): Nakagawa T, Suga S, Kawase T, Toda M
  • Journal Title: Brain Res 1089(1) Pages: 179-185
• [Journal Article] Development of cancer vaccine strategies for the treatment of brain tumors (2006)
  • Author(s): Toda M
  • Journal Title: Vaccines 26 Pages: 79-89
• [Journal Article] Enhancement of immunological tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and BCG-CWS stimulation (2006)
  • Author(s): Udagawa M, Hasegawa G, Yano K, Kudo C, Yamamoto A, Yaguchi M, Tsukamoto M, Toda M, Azuma I, Iwai T, Kawakami Y
  • Journal Title: Clin Cancer Res 12(24) Pages: 7465-7475
• [Journal Article] Cancer vaccine and immunotherapy for brain tumors
  • Author(s): Toda M, Kawakami Y
  • Journal Title: Curr Pharm Des in press
• [Presentation] Sox6の神経幹前駆細胞における発現および機能解析 (2007)
  • Author(s): 大多 茂樹、岡野 栄之、河瀬 斌、戸田 正博
  • Organizer: Neuro2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Sox6 is expressed in mouse embryonic neural stem/progenitor cells (NSPCs) and contributes to their maintenance and/or survival (2007)
  • Author(s): Shigeki, Ohta, Hidyuki, Okano, Takeshi, Kawase, Masahiro, Toda
  • Organizer: Neuro2007
  • Place of Presentation: Yokohama
  • Year and Date: 2007-09-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 霊長類モデルを用いた樹状細胞移植による神経損傷治療の解析 (2007)
  • Author(s): 戸田 正博、矢口 雅江、田伏 将尚、大多 茂樹、塚田 晃三、山根 淳一、中村 雅也、松崎 有末、谷岡 攻邦、河瀬 斌、戸山 芳昭、岡野 栄之
  • Organizer: 第28回 日本炎症、再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-03
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Analysis of functional recovery by the implantation of Dendritic cells in non-human primate (2007)
  • Author(s): Masahiro, Toda, Masae, Yaguchi, Masanao, Tabuse, Shigeki, Ohta, Kozo, Tsukada, Jun, Yamane, Masaya, Nakamura, Yumi, Matsuzaki, Yoshikuni, Tanioka, Takeshi, Kawase, Yoshiaki, Toyama, Hideyuki, Okano
  • Organizer: The Japanese society of Inflammation and regeneration, 28th meeting
  • Place of Presentation: Tokyo
  • Year and Date: 2007-08-03
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 霊長類モデルを用いた樹状細胞移植による神経損傷治療の解析 (2007)
  • Author(s): 戸田 正博、矢口 雅江、田伏 将尚、大多 茂樹、塚田 晃三、山根 淳一、中村 雅也、松崎 有末、谷岡 攻邦、河瀬 斌、戸山 芳昭、岡野 栄之
  • Organizer: 日本炎症再生学会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-03
• [Book] グリオーマ抗原SOX6ペプチドワクチンによる特異的免疫療法の開発 (2006)
  • Author(s): 植田良, 河瀬斌, 戸田正博
  • Total Pages: 5
  • Publisher: Surgery Frontier
• [Patent(Industrial Property Rights)] 神経幹細胞の分離方法及び増殖促進方法 (2008)
  • Inventor(s): 大多 茂樹、戸田 正博
  • Industrial Property Rights Holder: 学校法人慶應義塾大学
  • Industrial Property Number: 2008-014243
  • Filing Date: 2008-01-29
  • Description: 「研究成果報告書概要(和文)」より