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Establishing early embryonic development using naive pluripotent stem cells

Research Project

Project/Area Number 16H02465
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionKyoto University

Principal Investigator

Takashima Yasuhiro  京都大学, iPS細胞研究所, 講師 (70469930)

Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2020: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2018: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2017: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords発生分化 / 幹細胞 / 初期発生 / ナイーブ型ES細胞 / キメラ / 多能性幹細胞 / 原始内胚葉 / 栄養外胚葉 / 栄養膜幹細胞 / ヒトナイーブ型多能性幹細胞 / 再生医学 / 発生・分化 / ヒト / 霊長類
Outline of Final Research Achievements

Using naive human pluripotent stem cells (PSCs), we established a differentiation model from pre-implantation trophectoderm to syncytiotrophoblast and extravillous trophoblast via post-implantation cytotrophoblast (CT). In addition, we established a culture method to induce hypoblast and produced bilaminar disk-like structures (bilaminiods) by co-culturing human pre-implantation epiblast and our naive PSC-derived hypoblast. Hypoblast generated the basement membrane and polarity of epiblast, the pro-amniotic cavity, and the anterior-posterior axis. Epiblast started to express primitive streak genes. These observations all suggest we could model the pre-implantation to post-implantation transition of the human embryo in vitro.
Finally, we succeeded in establishing new primed and naive marmoset PSCs, finding some signaling pathways were conserved in humans and marmosets. This result emphasizes the importance of using monkey embryo data when evaluating human PSCs.

Academic Significance and Societal Importance of the Research Achievements

着床期の初期発生は、ヒト・非ヒト霊長類では不明な点が多く、マウスとも異なる。しかし、霊長類胚を用いた研究は、倫理面に対する問題を含み困難である。自身が報告したnaive型ヒト多能性幹細胞を用いて世界で初めて、栄養外胚葉から始まる胎盤細胞の分化モデルや二層性胚盤様構造(Bilaminoids)モデルを樹立した。ブラックボックスであったヒト初期発生を明らかにすることができ、今後幹細胞を用いたヒト初期発生研究分野を作りだす成果である。マーモセット胚を利用することで、非ヒト霊長類を用いた初期発生研究の基盤構築に成功した。霊長類研究の重要性を示すとともに不妊・発生異常にも貢献する意義が高い成果である。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (40 results)

All 2021 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 7 results,  Invited: 16 results) Book (2 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] IMBA(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Pluripotent stem cells for the study of early human embryology2021

    • Author(s)
      Semi Katsunori、Takashima Yasuhiro
    • Journal Title

      Development, Growth & Differentiation

      Volume: 63 Issue: 2 Pages: 104-115

    • DOI

      10.1111/dgd.12715

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Capturing human trophoblast development with naive pluripotent stem cells in vitro2021

    • Author(s)
      S Io M Kabata Y Lemura N Morone A Minagawa B Wong I Okamoto T Nakamura Y Kojima C Iwatani H Tsuchiya B Kawswandy E KondohS Kaneko K Woltjen M Saitou T Yamanoto M Mandai Y Takashima
    • Journal Title

      Cell Stem Cell

      Volume: 21 Issue: 6 Pages: 10-10

    • DOI

      10.1016/j.stem.2021.03.013

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis2019

    • Author(s)
      Huang M、Tailor J、Z Q、G AH、M ML、W H、C J、Z T、N EK.、M LK.、A Z、Y F、Takashima Y、Clarke J、A H、C FMG.、L B、M BS.、I S、C L、Y C、K KM.、M T、S N、K P、P SM.、D P、S MP、L DA、C YJ、P JJ、S FJ、M AS、K M、P SM、T MD、S A、W WA
    • Journal Title

      Cell Stem Cell

      Volume: 25 Issue: 3 Pages: 433-446.e7

    • DOI

      10.1016/j.stem.2019.05.013

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Reduced MEK inhibition preserves genomic stability in naive human embryonic stem cells2018

    • Author(s)
      Di Stefano Bruno、Ueda Mai、Sabri Shan、Brumbaugh Justin、Huebner Aaron J.、Sahakyan Anna、Clement Kendell、Clowers Katie J.、Erickson Alison R.、Shioda Keiko、Gygi Steven P.、Gu Hongcang、Shioda Toshi、Meissner Alexander、Takashima Yasuhiro、Plath Kathrin、Hochedlinger Konrad
    • Journal Title

      Nature Methods

      Volume: 15 Issue: 9 Pages: 732-740

    • DOI

      10.1038/s41592-018-0104-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.2018

    • Author(s)
      Yu, L.; Li, J.; Hong, J.; Takashima, Y.; Fujimoto, N.; Nakajima, M.; Yamamoto, A.; Dong, X.; Dang, Y.; Hou, Y.; Yang, W.; Minami, I.; Okita, K.; Tanaka, M.; Luo, C.; Tang, F.; Chen, Y.; Tang, C.; Kotera, H. & Liu, L.
    • Journal Title

      Stem Cell Reports

      Volume: 11 Issue: 1 Pages: 142-156

    • DOI

      10.1016/j.stemcr.2018.06.003

    • NAID

      120006488610

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surface markers guide the journey towards naive pluripotency2017

    • Author(s)
      Karagiannis P, Takashima Y
    • Journal Title

      Cell Stem Cell

      Volume: 20 Issue: 6 Pages: 237-238

    • DOI

      10.1016/j.stem.2017.05.004

    • Related Report
      2017 Annual Research Report
  • [Journal Article] History of Pluripotent Stem Cells and Human Naïve Pluripotent Stem Cells2017

    • Author(s)
      Ueda M, Takashima Y
    • Journal Title

      Cytometry Research

      Volume: 27 Issue: 1 Pages: 19-24

    • DOI

      10.18947/cytometryresearch.27.1_19

    • NAID

      130006832438

    • ISSN
      0916-6920, 2424-0664
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrimination of stem cell status after subjecting cynomolgus monkey pluripotent stem cells to naive conversion.2017

    • Author(s)
      Honda A, Kawano Y, Izu H, Choijookhuu N, Honsho K, Nakamura T, Yabuta Y, Yamamoto T, Takashima Y, Hirose M, Sankai T, Hishikawa Y, Ogura A, Saitou M
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 45285-45285

    • DOI

      10.1038/srep45285

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ナイーブ型iPS細胞の可能性と課題2021

    • Author(s)
      高島康弘
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ナイーブ型ヒトiPS細胞研究に関するアップデート2020

    • Author(s)
      高島康弘
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ナイーブ型iPS細胞とヒトES/iPS細胞運命制御の基盤を理解する2020

    • Author(s)
      高島康弘
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ナイーブ型ヒトiPS細胞研究に関するアップデート2020

    • Author(s)
      高島康弘
    • Organizer
      日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ナイーブ型多能性幹細胞を利用したヒト着床期発生2020

    • Author(s)
      高島康弘
    • Organizer
      第43回 日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Modeling in vitro embryonic development using naive pluripotent stem cells2020

    • Author(s)
      高島康弘
    • Organizer
      第10回日本マーモセット研究大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 着床前から着床期にかけてのヒト・霊長類発生を明らかにする2019

    • Author(s)
      高島康弘
    • Organizer
      第42回日本分子生物学会年会日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒトナイーブ型多能性幹細胞とヒト初期発生2019

    • Author(s)
      高島康弘
    • Organizer
      第17回幹細胞シンポジウム幹細胞シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Establishment of primitive endoderm cells from human pluripotent stem cells2019

    • Author(s)
      大久保巧 高島康弘
    • Organizer
      第17回幹細胞シンポジウム幹細胞シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Reconstituting primitive haematopoiesis using human naive pluripotent stem cells2019

    • Author(s)
      大久保巧 高島康弘
    • Organizer
      第42回日本分子生物学会年会日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Challenges to induction of naive-state pluripotent stemcells in non-human primate2019

    • Author(s)
      蝉 克憲, 高島 康弘
    • Organizer
      第8回マーモセット研究会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトナイーブ型iPS細胞を用いてヒト初期発生を解析する2018

    • Author(s)
      高島 康弘
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 実用化に向けたヒトナイーブ型iPS細胞に関する最新知見2018

    • Author(s)
      高島 康弘
    • Organizer
      BioJapan2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の誕生・現在・未来―iPS細胞を若返らせるー2018

    • Author(s)
      高島 康弘
    • Organizer
      日本アンチエイジング歯科学会第13回学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Primitive endoderm specification from naive pluripotent stem cells in human2018

    • Author(s)
      高島 康弘
    • Organizer
      From stem cell to human development
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pluripotent stem cells in human and common marmoset2018

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      Japan Society for marmoset research, International symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトナイーブ型多能性幹細胞を用いた再生医療研究とヒト初期発生モデル2018

    • Author(s)
      高島 康弘
    • Organizer
      Molecular Diabetology Coference
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Diiferentiation competence in human naive pluripotente stem cells2017

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      CiRA 2017 International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトナイーブ型多能性幹細胞と分化2017

    • Author(s)
      高島 康弘
    • Organizer
      第40回 日本分子生物学会(ConBio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 霊長類における初期発生と多能性幹細胞2017

    • Author(s)
      高島 康弘
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DERIVATION OF COMMON MARMOSET PRIMED ES CELLS UNDER HUMAN PRIMED ES CELL CURTURE CONDITION2017

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      15th ISSCR Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトナイーブ型多能性幹細胞2016

    • Author(s)
      高島 康弘
    • Organizer
      第26回日本サイトメトリー学会学術集会
    • Place of Presentation
      九州
    • Year and Date
      2016-07-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ナイーブ型多能性幹細胞2016

    • Author(s)
      高島 康弘
    • Organizer
      第63回日本実験動物学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Looking at naive and primed human pluripotent stem cells from the point of view of ageing2016

    • Author(s)
      Y Takashima
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Santa Fe, New Mexico, USA
    • Year and Date
      2016-05-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] マーモセットラボマニュアル : はじめての取扱いから研究最前線まで2018

    • Author(s)
      蝉 克憲、島田 亜樹子、高島康弘
    • Total Pages
      230
    • Publisher
      アドスリー
    • ISBN
      4904419782
    • Related Report
      2018 Annual Research Report
  • [Book] iPS細胞の樹立とあらたな生命科学の開拓2016

    • Author(s)
      高島康弘、山中伸弥
    • Total Pages
      4
    • Publisher
      医学のあゆみ
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] NAIVE HUMAN PSC-DERIVED HYPOBLAST REGULATE THE EPIBLASTTRANSITIONS DURING PERI-IMPLANTATION2020

    • Inventor(s)
      高島 康弘、大久保 巧
    • Industrial Property Rights Holder
      高島 康弘、大久保 巧
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ナイーブ型多能性幹細胞からの栄養外胚葉誘導方法2019

    • Inventor(s)
      高島康弘、伊尾慎吾
    • Industrial Property Rights Holder
      高島康弘、伊尾慎吾
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-212446
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 多能性幹細胞からの造血細胞の製造方法2019

    • Inventor(s)
      高島康弘、大久保巧
    • Industrial Property Rights Holder
      高島康弘、大久保巧
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-214919
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] ナイーブ型多能性幹細胞からの原始内胚葉誘導方法2018

    • Inventor(s)
      高島康弘、大久保 巧、蝉 克憲
    • Industrial Property Rights Holder
      高島康弘、大久保 巧、蝉 克憲
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ナイーブ型多能性幹細胞からの原始内胚葉誘導方法2017

    • Inventor(s)
      高島康弘 大久保巧 蝉克憲
    • Industrial Property Rights Holder
      高島康弘 大久保巧 蝉克憲
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-215115
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2023-01-30  

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