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α1,3フコース転移酵素Fut10による幹細胞の未分化性維持機構の解明

Publicly Offered Research

Project AreaDeciphering sugar chain-based signals regulating integrative neuronal functions
Project/Area Number 26110710
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionShiga University of Medical Science

Principal Investigator

等 誠司  滋賀医科大学, 医学部, 教授 (70300895)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
KeywordsLewisX / 幹細胞 / 未分化性 / 網膜 / 神経幹細胞 / LewisX抗原 / N結合型糖鎖
Outline of Annual Research Achievements

神経幹細胞は、発達期の脳において全ての神経細胞・グリア細胞を産生するのみならず、成体脳にも存在して脳機能に重要な役割を果たす。しかし、神経幹細胞が終生に亙って未分化性を維持し、かつ適切な時期に細胞を分化させて神経ネットワークを構築する分子機構には、不明な点が多い。本研究は、幹細胞の未分化性に密接に係わる糖鎖であるLex抗原に注目した。これまで、脳におけるLex抗原を生合成する酵素はFut9だと考えられていたが、Fut9ノックアウトマウスがほぼ正常に発生・発達し、脳にも大きな異常が観察されないことが大きな矛盾点であった。研究代表者は、独自の視点から、神経幹細胞特異的に発現する新規の_1,3-フコース転移酵素Fut10を同定し、幹細胞の未分化性維持に働いていることを明らかにした。本研究では、Fut10の基質特異性などの酵素学的解析や、Fut10が生合成するLex抗原を含有する糖鎖の同定を行うことで、神経幹細胞の未分化性維持のメカニズムを明らかにする。
平成26年度までに、ES細胞や神経幹細胞でFut10遺伝子を過剰発現/機能喪失させ、その表現型を解析した。その結果、Fut10遺伝子の過剰発現で未分化性が亢進し、ノックダウンでは逆に分化が促進されることを明らかにした。平成27年度は、Fut10遺伝子の過剰発現/ノックアウトES細胞やノックアウトマウスの作製・解析を行った結果、Fut10が内胚葉や神経の発生を制御することを示唆するデータを得た。また、興奮性神経毒による網膜神経細胞の修復過程においても、Fut10が重要な役割を担うことを明らかにした。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (16 results)

All 2016 2015 2014 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] The dorsoventral boundary of the germinal zone is a specialized niche for the generation of cortical oligodendrocytes during a restricted temporal window.2016

    • Author(s)
      Naruse M, Ishino Y, Kumar A, Ono K, Takebayashi H, Yamaguchi M, Ishizaki Y, Ikenaka K, Hitoshi S
    • Journal Title

      Cerebral Cortex

      Volume: 26

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural stem cells and neuro/gliogeneis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.2016

    • Author(s)
      Yamaguchi M, Seki T, Imayoshi I, Tamamaki N, Hayashi Y, Tatebayashi Y, Hitoshi S
    • Journal Title

      Journal of Physiological Sciences

      Volume: 66

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterozygous Polg mutation causes motor dysfunction due to mtDNA deletions.2014

    • Author(s)
      Fuke S, Kametani M, Yamada K, Kasahara T, Kubota-Sakashita M, Kujoth GC, Prolla TA, Hitoshi S, Kato T
    • Journal Title

      Annals of Clinical and Translational Neurology

      Volume: 1 Issue: 11 Pages: 909-920

    • DOI

      10.1002/acn3.133

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Determination of major sialylated N-glycans and identification of branched sialylated N-glycans that dynamically change their content during development in the mouse cerebral cortex.2014

    • Author(s)
      Torii T, Yoshimura T, Narumi M, Hitoshi S, Takaki Y, Tsuji S, Ikenaka K
    • Journal Title

      Glycoconjugate Journal

      Volume: 31(9) Pages: 671-683

    • DOI

      10.1007/s10719-014-9566-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.2014

    • Author(s)
      Zheng LS, Hitoshi S, Kaneko N, Takao K, Miyakawa T, Tanaka Y, Xia H, Kalinke U, Kudo K, Kanba S, Ikenaka K, Sawamoto K.
    • Journal Title

      Stem Cell Reports

      Volume: 3(1) Issue: 1 Pages: 73-84

    • DOI

      10.1016/j.stemcr.2014.05.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The Lewis X-related α1,3-fucosyltransferase, Fut10, is required for the maintenance of stem cell populations.2015

    • Author(s)
      Hitoshi S
    • Organizer
      BMB2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The dorsoventral boundary of the germinal zone is a specialized niche for the generation of cortical oligodendrocytes.2015

    • Author(s)
      Hitoshi S, Asuke J, Naruse M, Ikenaka K
    • Organizer
      第58回日本神経化学会
    • Place of Presentation
      大宮
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Epigenetics in the maintenance of neural stem cells.2015

    • Author(s)
      Hitoshi S
    • Organizer
      25th Meeting of the International Society for Neurochemistry
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経幹細胞からオリゴデンドロサイト系譜細胞が産生される分子機序2015

    • Author(s)
      等 誠司, 成瀬雅衣, 池中一裕
    • Organizer
      第120回日本解剖学会・第92回日本生理学会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The Lewis X-related α1,3-fucosyltransferase, Fut10, is required for the maintenance of stem cell populations.2014

    • Author(s)
      Hitoshi S, Fuke S, Kumar A, Ikenaka K
    • Organizer
      Society for Glycobiology & Japanese Society of Carbohydrate Research 2014 Joint Annual Meeting
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Relationship between cortical neurogenesis and mood; a study of primate.2014

    • Author(s)
      Hayashi Y, Fuke S, Fuchigami T, Koyama N, Tatebayashi Y, Hitoshi S
    • Organizer
      第57回日本神経化学会, 第36回日本生物学的精神医学会 合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analysis of the mono-ubiquitylation of histone H2B associated with differentiation into neural stem cell linage.2014

    • Author(s)
      Fuke S, Ishino Y, Hayashi Y, Nakabayashi K, Ikenaka K, Hitoshi S
    • Organizer
      第57回日本神経化学会, 第36回日本生物学的精神医学会 合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] The effects of maternal separation on the anxiety- and fear-related behavior in the mice.2014

    • Author(s)
      Koyama N, Jia X, Hitoshi S
    • Organizer
      第37回日本神経科学学会 (Neuroscience 2014)
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Epigenetic mechanisms underlying the generation and differentiation of neural stem cells.2014

    • Author(s)
      Hitoshi S, Hayashi Y, Fuchigami T, Fuke S, Ishino Y, Ikenaka K
    • Organizer
      12th Annual Meeting of the International Society for Stem Cell Research
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2014-06-18 – 2014-06-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 恐怖回避モデルの動物モデル探索のための予備的研究2014

    • Author(s)
      小山なつ, 賈 暁静, 福家 聡, 等 誠司
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Remarks] 統合臓器生理学部門 研究内容

    • URL

      http://www.shiga-med.ac.jp/~hqphysi1/physiol1/research/index-re.html

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-28  

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