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Elucidation of the vascular niche for the neural stem cells

Research Project

Project/Area Number 26460360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionUniversity of Toyama

Principal Investigator

Yamamoto Seiji  富山大学, 大学院医学薬学研究部(医学), 助教 (10456361)

Co-Investigator(Kenkyū-buntansha) 笹原 正清  富山大学, 大学院医学薬学研究部(医学), 教授 (20154015)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血管 / 神経幹細胞 / EV / niche / RTKシグナル / miRNA / 神経
Outline of Final Research Achievements

It has been known that adult brain has neural stem cells residing in the niche such as subventricular zone. Cerebral blood vessels are considered to be a source of soluble factors to interact with neural stem cells (NSCs). To clarify this, we conducted coculture experiment using cerebral blood vessel derived endothelial cell line and NSCs. We found that endothelial cell derived extracellular vesicles (E-EVs) included many kind of micro RNAs (miRNAs). In silico and in vitro studies showed that some of them could suppress the expression level of transcription factors that play an important role in neuronal differentiation. By real-time PCR analyses, the endothelial cell line produced a ligand that can activate a receptor type tyrosine kinase (RTK) expressed on the NSCs. Accordingly, we conclude that cerebral endothelial cells supply the two types of soluble factors as a niche for NSCs, which are miRNAs included in E-EVs and the ligand for activating the RTK.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (28 results)

All 2016 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice.2016

    • Author(s)
      Watanabe Y, Nagai Y, Honda H, Okamoto N, Yamamoto S, Hamashima T, Ishii Y, Tanaka M, Suganami T, Sasahara M, Miyake, K, Takatsu K.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 23097-23097

    • DOI

      10.1038/srep23097

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PDGFR-β Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke.2016

    • Author(s)
      Sato H, Ishii Y, Yamamoto S, Azuma E, Takahashi Y, Hamashima T, Umezawa A, Mori H, Kuroda S, Endo S, Sasahara M.
    • Journal Title

      Stem Cells.

      Volume: 34 Issue: 3 Pages: 685-698

    • DOI

      10.1002/stem.2212

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glioma-derived PDGF-BB recruits oligodendrocyte progenitor cells via PDGFRα and remodels cancer stroma2016

    • Author(s)
      Zheng Y, Yamamoto S, Ishii Y, Sang Y, Hamashima T, De VN, Nishizono H, Inoue R, Mori H, Sasahara M.
    • Journal Title

      The American Journal of Pathology

      Volume: 34 Issue: 5 Pages: 685-698

    • DOI

      10.1016/j.ajpath.2015.12.020

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki Disease2016

    • Author(s)
      Saito K, Nakaoka H, Takasaki I, Hirono K, Yamamoto S, Kinoshita K, Miyao N, Ibuki K, Ozawa S, Watanabe K, Bowles NE, Ichida F
    • Journal Title

      Pediatr Res

      Volume: 80 Issue: 3 Pages: 425-432

    • DOI

      10.1038/pr.2016.93

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance.2016

    • Author(s)
      Takikawa A, Mahmood A, Nawaz A, Kado T, Okabe K, Yamamoto S, Arif A, Senda S, Tsuneyama K, Ikutani M, Watanabe Y, Igarashi Y, Nagai Y, Takatsu K, Koizumi K, Imura J, Goda N, Sasahara M, Matsumoto M, Saeki K, Nakagawa T, Fujisaka S, Usui I, Tobe K.
    • Journal Title

      Diabetes

      Volume: 65(12) Issue: 12 Pages: 3649-3659

    • DOI

      10.2337/db16-0012

    • NAID

      40021380120

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inflammation-induced endothelial cell-derived extracellukar vesicles modulate the cellular status of pericytes.2015

    • Author(s)
      Yamamoto S., Niida S., Azuma E., Yanagibashi T., Muramatsu M., Huang TT., Sagara H., Higaki S., Ikutani M., Nagai Y., Takatsu K., Miyazaki K., Hamashima T., Mori H., Matsuda N., Ishii Y., Sasahara M.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 8505-8505

    • DOI

      10.1038/srep08505

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of power-law growth in the self-renewal of heterogeneous glioma stem cell populations.2015

    • Author(s)
      Sugimori, M., Hayakawa, H., Boman, B.M., Fields, J.Z., Awaji, M., Kozano, H., Tamura, R., Yamamoto, S., Ogata, T., Yamada, M., Endo, S., Kurimoto, M. and Kuroda, S.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 8 Pages: e0135760-e0135760

    • DOI

      10.1371/journal.pone.0135760

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PDGFRα plays a crucial role in connective tissue remodeling.2015

    • Author(s)
      Horikawa S, Ishii Y, Hamashima T, Yamamoto S, Mori H, Fujimori T, Shen J, Inoue R, Nishizono H, Itoh H, Majima M, Abraham D, Miyawaki T, Sasahara M.
    • Journal Title

      Scientific Reports

      Volume: Dec 7;5 Issue: 1 Pages: 17948-17948

    • DOI

      10.1038/srep17948

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] PDGFRβ plays an important role in the ectopic migration of neuroblasts in association with blood vessels in cerebral stroke2016

    • Author(s)
      Yamamoto S, Azuma E, Ishii Y, Hamashima T, Sato H, Sasahara M
    • Organizer
      The 14th Korea-Japan Joint Symposium on Vascular Biology
    • Place of Presentation
      Nagasaki, Japan
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中枢神経系ペリサイトの起源に迫る2016

    • Author(s)
      山本誠士
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] PDGFRβ plays a key role in the ectopic migration of neuroblasts along with blood vessels in cerebral stroke2016

    • Author(s)
      Yamamoto S, Ishii Y, Hamashima T, Sato H, Azuma E, Sasahara M
    • Organizer
      The 19th International Vascular Biology Meeting
    • Place of Presentation
      Boston, Massachusetts, USA
    • Year and Date
      2016-10-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Developed novel rodent model of diabetic retinopathy after conditional Pdgfrb gene targeting2016

    • Author(s)
      Kitahara H, Yamamoto S, Kajikawa S, Azuma E, Hamashima T, Ishii Y, Sato H, Shimada Y, Sasahara M
    • Organizer
      The 19th International Vascular Biology Meeting
    • Place of Presentation
      Boston, Massachusetts, USA
    • Year and Date
      2016-10-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経前駆細胞の脳梗塞部位への遊走におけるPDGFRβシグナルの重要性2016

    • Author(s)
      山本誠士, 石井陽子, 濱島丈, 佐藤光, 東英梨月, 笹原正清
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] PDGFR-β plays a key role in the ectopic migration of neuroblasts in cerebral stroke2016

    • Author(s)
      Satou H, Yamamoto S, Kuroda S, Sasahara M, Watanabe S, Watanabe K
    • Organizer
      5th Mt.BANDAI & Pan-Pacific Joint Neurosurgical Convention
    • Place of Presentation
      Phnom Penh, Cambodia
    • Year and Date
      2016-04-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管炎症モデルにおける血管内皮細胞とペリサイトのインタラクション2015

    • Author(s)
      山本誠士
    • Organizer
      第23回日本血管生物医学会学術集会(CVMW2015)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 神経発生期における血球系由来ペリサイトの動態2015

    • Author(s)
      山本誠士
    • Organizer
      第38回日本分子生物学会年会(BMB2015)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] M2-like macrophages contribute to angiogenesis in skin wound healing process2015

    • Author(s)
      8.東英梨月, 山本誠士, 村松昌, 濱島丈, 石井陽子, 藤原章雄, 竹屋元裕, 新飯田俊平, 笹原正清
    • Organizer
      第38回日本分子生物学会年会(BMB2015)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Analysis of the inflammation related miRNA encapsulated in the endothelial derived extracellular vesicles2015

    • Author(s)
      Yamamoto S
    • Organizer
      The 13th Japan-Korea Joint Symposium on Vascular Biology
    • Place of Presentation
      Busan, Korea
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス創傷治癒モデルにおける多機能型マクロファージの解析2015

    • Author(s)
      12.山本誠士, 東英梨月, 村松昌, 濱島丈, 石井陽子, 新飯田俊平, 笹原正清
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Secreted miRNA plays an important role in the endothelial vascular niche2014

    • Author(s)
      Yamamoto S, Azuma E, Hamashima T, Ishii Y, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Multifunctional macrophages contribute to angiogenesis and vascular homeostasis in skin wound healing site2014

    • Author(s)
      Azuma E, Yamamoto S, Muramatsu M, Hamashima T, Ishii Y, Niida S, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Redirected migration of the DCX+ cells guided by blood vessels toward ischemic core2014

    • Author(s)
      Sato H, Yamamoto S, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] PDGFR-alpha is essential for the connective tissue remodelling2014

    • Author(s)
      Horikawa S, Yamamoto S, Hamashima T, Ishii Y, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] PDGFR-alpha regulates the dynamism of oligodendrocytes through recruitment of perivascular mesenchymal stem cells in the adult mouse brain2014

    • Author(s)
      Dang TC, Ishii Y, Yamamoto S, Hamashima T, Ohkawa N, Saitoh Y, Inokuchi K, Mori H, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] PDGF receptor dimers drive distinct migration of the mouse skin fibroblast2014

    • Author(s)
      Yamada K, Yamamoto S, Hamashima T, Ishii Y, Noguchi M, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Involvement of PDGFR-beta in blood-brain barrier function after cerebral ischemia2014

    • Author(s)
      Shen J, Ishii Y, OuYang X, Yuan J, Zhu R, Xu G, Dang TC, Hamashima T, Matsushima T, Yamamoto S, Sasahara M
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Remarks] 富山大学 病態病理学

    • URL

      http://www.med.u-toyama.ac.jp/pathol2/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] Department of Pathology, University of Toyama

    • URL

      http://www.med.u-toyama.ac.jp/pathol2/index.html

    • Related Report
      2015 Research-status Report 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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