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Induction of hematopoietic stem/progenitor cells from mouse pluripotent stemceIIsby inhibitionofanadaptor protein, Lnk.

Research Project

Project/Area Number 23790123
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research Institution独立行政法人医薬基盤研究所

Principal Investigator

TASHIRO Katsuhisa  独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, 研究員 (30580138)

Research Collaborator KAWABATA Kenji  独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, プロジェクトリーダー
MIZUGUCHI Hiroyuki  大阪大学, 大学院・薬学研究科, 教授
SAKURAI Fuminori  大阪大学, 大学院・薬学研究科, 准教授
YAMAGUCHI Tomoko  独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, プロジェクト研究員
OMORI Miyuki  大阪大学, 大学院・薬学研究科, 大学院生
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsES細胞 / ips細胞 / 血液細胞 / 再生医学 / 多能性幹細胞 / 分化誘導 / 幹細胞
Research Abstract

The adaptor protein Lnk is shown to negatively regulate HSPC function and HSPCs derived from Lnk-deficient mice show enhanced self-renewal and repopulation capacity. In this study, we attempted to generate hematopoietic cells including HSPCs from mouse embryonic stem(ES)cells and induced pluripotent stem(iPS)cells by inhibition of Lnk function using a dominant-negative mutant of Lnk(DN-Lnk)gene. We showed that Lnk inhibition in mouse ES cells and iPS cells resulted in more efficient generation of mesodermal cells and hematopoietic cells than control cells. Lnk inhibition by the transduction of DN-Lnk gene augmented the thrombopoietin-induced phospholylation of Jak2, Erk1/2, and Akt, indicating the enhanced sensitivity to TPO. Thus, our data clearly showed that inhibition of Lnk in ES cells and iPS cells could lead to efficient generation and expansion of immature hematopoietic cells.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2013 2012 2011

All Journal Article (7 results) (of which Peer Reviewed: 1 results) Presentation (8 results)

  • [Journal Article] Two-step differentiation of mast cells from induced pluripotent stem cells2013

    • Author(s)
      Yamaguchi T., Tashiro K, Tanaka S Katayama S., Ishida W., Fukuda K., Fukushima A., Araki R., Abe M., Mizuguchi H., Kawabata K
    • Journal Title

      Stem Cells Dev

      Volume: 22(5) Pages: 726-734

    • Related Report
      2012 Final Research Report
  • [Journal Article] Inhibition of Lnk in mouse induced pluripotent stem cells promotes hematopoietic cell generation2012

    • Author(s)
      Tashiro K, Omori M, Kawabata K, Hirata N., Yamaguchi T., Sakurai F., Takaki S., Mizuguchi H
    • Journal Title

      Stem Cells Dev

      Volume: 21(18) Pages: 3381-3390

    • Related Report
      2012 Final Research Report
  • [Journal Article] The promotion of hepatic maturation of human pluripotent stem cells in 3D co-culture using Type I collagen and Swiss 3T3 cell sheets.2012

    • Author(s)
      Nagamoto Y, Tashiro K., Takayama K, Ohashi K., Kawabata K., Sakurai F., Tachibana M., Hayakawa T., Furue MK, Mizuguchi H
    • Journal Title

      Biomaterials

      Volume: 33(18) Pages: 4526-4534

    • Related Report
      2012 Final Research Report
  • [Journal Article] Efficient Generation of Functional Hepatocytes from Human Embryonic Stem Cells and Induced luripotent Stem Cells by HNF4αTransduction2012

    • Author(s)
      Takayama K, Inamura M., Kawabata K., Katayama K, Higuchi M., Tashiro K, Nonaka A., Sakurai F., Hayakawa T., Furue MK., Mizuguchi H
    • Journal Title

      Mol. Ther

      Volume: 20(1) Pages: 127-137

    • Related Report
      2012 Final Research Report
  • [Journal Article] Promotion of hematopoietic differentiation from mouse induced pluripotent stem cells by transient HoxB4 transduction2012

    • Author(s)
      Tashiro K., Kawabata K., Omori M., Yamaguchi T., Sakurai F., Katayama K, Hayakawa T., Mizuguchi H
    • Journal Title

      Stem Cell Res

      Volume: 8(2) Pages: 300-311

    • Related Report
      2012 Final Research Report
  • [Journal Article] Inhibition of Lnk in mouse induced pluripotent stem cells promotes hematopoietic cell generation.2012

    • Author(s)
      Tashiro K, Omori M, Kawabata K, Hirata N, Yamaguchi T, Sakurai F, Takaki S, Mizuguchi H
    • Journal Title

      Stem Cells Dev.

      Volume: 21 Issue: 18 Pages: 3381-3390

    • DOI

      10.1089/scd.2012.0100

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimization of adenovirus vectors for transduction in embryonic stem cells and induced pluripotent stem cells2011

    • Author(s)
      Tashiro K
    • Journal Title

      Yakugaku Zasshi

      Volume: 131(9) Pages: 1333-1338

    • NAID

      130001871940

    • Related Report
      2012 Final Research Report
  • [Presentation] アダプター蛋白質Lnkの抑制はマウスES/iPS細胞から血液前駆細胞への分化を促進する2013

    • Author(s)
      田代 克久、大森 美幸、川端 健二、平田 信恵、山口 朋子、櫻井 文教、高木 智、水口 裕之
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] マウスips細胞から成熟したマスト細胞の分化誘導法の開発2013

    • Author(s)
      山口 朋子、田代 克久、田中 智之、水口 裕之、川端 健二
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] マスト細胞の成熟化に関与する新規液性因子の同定2012

    • Author(s)
      山口 朋子、田代 克久、田中 智之、水口 裕之、川端 健二
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] Es/iPs細胞由来肝細胞のswiss 3T3細胞との積層3次元共培養下における成熟化・促進機構の解析2012

    • Author(s)
      長基 康人、田代 克久、高山 和雄、大橋 一夫、岡野 光夫、櫻井 文教、立花 雅史、古江一楠田 美保、川端 健二、水口 裕之
    • Organizer
      第19回大会肝細胞研究会
    • Place of Presentation
      札幌
    • Related Report
      2012 Final Research Report
  • [Presentation] Enhanced hematopoietic differentiation from mouse embryonic stem cells and induced pluripotent stem cells by inhibition of an adaptor protein, Lnk2012

    • Author(s)
      Katsuhisa Tashiro, Tomoko『Yamaguchi, Kenji Kawabata, Satoshi Takaki, Hiroyuki Mizuguchi
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2012 Final Research Report
  • [Presentation] 幹細胞への高効率遺伝子導入技術を利用した分化誘導法の開発2011

    • Author(s)
      田代 克久、川端 健二、櫻井 文教、水口 裕之
    • Organizer
      第61回日本薬学会近畿支部総会・大会
    • Place of Presentation
      神戸
    • Year and Date
      2011-10-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 幹細胞への高効率遺伝子導入技術を利用した分化誘導法の開発2011

    • Author(s)
      田代克久、川端健二、櫻井文教、水口裕之
    • Organizer
      第61回日本薬学会近畿支部総会・大会(招待講演)
    • Place of Presentation
      神戸
    • Related Report
      2011 Research-status Report
  • [Presentation] Enhanced hematopoietic differentiation from mouse embryonic stem cells and induced pluripotent stem cells by inhibition of an adaptor protein, Lnk.2011

    • Author(s)
      Katsuhisa Tashiro, Tomoko Yamaguchi, Kenji Kawabata, Satoshi Takaki, Hiroyuki Mizuguchi
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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