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Mechanisms underlying differentiation of human pluripotent stem cells into peripheral neurons

Research Project

Project/Area Number 15K11035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionKyoto University (2017)
National Institutes of Biomedical Innovation, Health and Nutrition (2015-2016)

Principal Investigator

Suga Mika  京都大学, iPS細胞研究所, 特定研究員 (00340448)

Co-Investigator(Kenkyū-buntansha) 金 美海  大阪大学, 工学研究科, 准教授 (30506449)
古江 美保  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ヒト幹細胞応用開発室, 招へいプロジェクトリーダー (80257310)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経堤 / 末梢神経 / ヒト多能性幹細胞 / 頭部神経堤細胞 / 分化誘導 / ヒトiPS細胞 / ヒトES細胞
Outline of Final Research Achievements

To understand the molecular mechanisms underlying peripheral nerve system development, we conducted in vitro differentiation of human pluripotent stem cells into ectoderm, neural epithelium, neural crest, and peripheral neurons.Neural crest cells and peripheral neurons were induced by controling medium conposition and culture surface, using growth factors, inhibitors, and extracellular matrixes.The results suggest the mechanisms underlying peripheral nerve development.

Academic Significance and Societal Importance of the Research Achievements

末梢神経細胞は神経堤(Neural Crest)から発生するが、神経堤は、脊椎動物の発生過程で一過性に現れる細胞群であり、解析が困難であるため、末梢神経系の細胞の分化メカニズムは中枢神経系の細胞に比べても不明な部分が多い。培養皿でヒト多能性幹細胞から神経堤、末梢神経への分化を再現することは、末梢神経系の細胞の分化メカニズムの解明をするために有効な方法である。本研究では、種々の増殖因子やインヒビター、細胞外マトリックスを組み合わせて培地添加因子ならびに培養面を精密にコントロールすることにより神経堤細胞、末梢神経細胞へと誘導し、末梢神経細胞の分化メカニズムを示唆する結果が得られた。

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Int'l Joint Research: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] High cell density suppresses BMP4-induced differentiation of human pluripotent stem cells to produce macroscopic spatial patterning in a unidirectional perfusion culture chamber.2018

    • Author(s)
      Tashiro S, Le MNT, Kusama Y, Nakatani E, Suga M, Furue MK, Satoh T, Sugiura S, Kanamori T, Ohnuma K.
    • Journal Title

      J Biosci Bioeng.

      Volume: 印刷中 Issue: 3 Pages: 379-388

    • DOI

      10.1016/j.jbiosc.2018.03.007

    • NAID

      40021667204

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and Expansion of Human Pluripotent Stem Cell-derived Hepatic Progenitor Cells by Growth Factor Defined Serum-free Culture Conditions2017

    • Author(s)
      Fukuda T., Takayama K., Hirata M., Liu Y., Yanagihara K., Suga M., Mizuguchi H., Furue M.
    • Journal Title

      Experimental Cell Research

      Volume: 352 Issue: 2 Pages: 333-345

    • DOI

      10.1016/j.yexcr.2017.02.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vitro Models of Cranial Neural Crest Development toward Toxicity Tests: Frog, Mouse and Human.2016

    • Author(s)
      Suga M, Hayashi Y, Furue MK.
    • Journal Title

      Oral Dis.

      Volume: - Issue: 5 Pages: 559-565

    • DOI

      10.1111/odi.12523

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Imaging-cytometry revealed spatial heterogeneities of marker expression in undifferentiated human pluripotent stem cells2016

    • Author(s)
      M. Suga, S. Tachikawa, D. Tateyama, K. Ohnuma, M.K. Furue
    • Journal Title

      In Vitro Cellular & Developmental Biology-Animal

      Volume: 53 Issue: 1 Pages: 83-91

    • DOI

      10.1007/s11626-016-0084-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of differentiation tendency toward hepatocytes from gene expression in undifferentiated human pluripotent stem cells.2016

    • Author(s)
      Yanagihara K, Liu Y, Kanie K, Okamura M, Hirata M, Fukuda T, Suga M, Nikawa H, Kato R, Furue MK.
    • Journal Title

      Stem cells and development.

      Volume: 25(24) Issue: 24 Pages: 1884-1897

    • DOI

      10.1089/scd.2016.0099

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells.2016

    • Author(s)
      Mimura S, Suga M, Okada K, Kinehara M, Nikawa H, Furue MK.
    • Journal Title

      Int J Dev Biol.

      Volume: 60 Issue: 1-2-3 Pages: 21-28

    • DOI

      10.1387/ijdb.160040mk

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ヒトiPS細胞由来頭部神経堤様細胞を用いたin vitro発生毒性試験法の構築に関する基礎的研究2017

    • Author(s)
      菅三佳、 三村純代 、 劉有容、中野貴子、二川浩樹、古江―楠田美保
    • Organizer
      日本動物代替法学会第30回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Noninvasive Live Cell Imaging Assays for Toxicity Prediction Using Neuroepithelial-like Stem Cells Derived from Human iPS Cells2017

    • Author(s)
      Mika Suga, Hiroaki Kii, Naoko Ueda , Takako Nakano, Yu-Jung Liu, Takayuki Uozumi , Tomoro Dan, Yasujiro Kiyota, and Miho K. Furue
    • Organizer
      SOT2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Role Of The Signaling Factors On Differentiation Of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells2016

    • Author(s)
      Suga M., Mimura S., Okada K., Kinehara M., Nikawa H., and Furue MK.
    • Organizer
      ISSCR 2016 ANNUAL MEETING
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE ROLE OF THE SIGNALING FACTORS ON DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELL-DERIVED NEURAL CREST STEM CELLS2016

    • Author(s)
      Mika Suga, Sumiyo Mimura, Masaki Kinehara, Hiroki Nikawa and Miho Kusuda Furue
    • Organizer
      ISSCR2016
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2016-06-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a New Cell-based Assay Using Human ES/iPS Cell-derived Neural Stem Cells for Developmental Neurotoxicity (DNT) Testing.2016

    • Author(s)
      Suga M., Kii H., Uozumi T., Kiyota Y, Furue MK
    • Organizer
      World Congress on In VItro Biology
    • Place of Presentation
      サンディエゴ
    • Year and Date
      2016-06-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a new cell-based-assay using human ES/iPS cell derived neural stem cells for developmental neurotoxicity testing.2016

    • Author(s)
      Suga M., Kii H,Uozumi T,Kiyota Y, Furue MK.
    • Organizer
      日本組織培養学会第89回大会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2016-05-25
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 神経幹細胞の製造方法、培地、サプリメント、サプリメントセット、 培地キット、及び細胞培養装置2017

    • Inventor(s)
      古江美保、菅三佳、紀伊宏昭、魚住孝之、清田泰次郎
    • Industrial Property Rights Holder
      古江美保、菅三佳、紀伊宏昭、魚住孝之、清田泰次郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2023-01-30  

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