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Totipotency conserved in primates and rodents

Research Project

Project/Area Number 21K19189
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionKyoto University

Principal Investigator

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

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords多能性幹細胞 / 全能性 / 胚体外細胞 / 未分化 / ナイーブ型多能性幹細胞 / 8細胞期 / マーモセット / 霊長類 / 卵割期様細胞
Outline of Research at the Start

人工多能性幹(iPS)細胞の樹立によって、転写因子セットを体細胞に導入することで、動物細胞も多能性を持った細胞へとリプログラミング可能であることが示された。しかしiPS細胞は多能性幹細胞であり全能性細胞ではない。本研究では霊長類の全能性を解析する。本提案は、受精卵がもつ全能性という生命の根源と始まりを今までアプローチできなかったヒトを含む霊長類において解析し、げっ歯類との比較解析を行う。

Outline of Final Research Achievements

Totipotency is the ability of a fertilized egg to differentiate into all types of cells including extraembryonic cells that make up an individual. Mouse ES cells, which belong to rodents, are considered to be pluripotent stem cells (PSCs) because they can not differentiate into the trophoblast lineage of the placenta. In this study, however, we were able to induce naive human ES/iPS cells to the trophectoderm of blastocysts at the pre-implantation stage. Furthermore, we succeeded in inducing cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast, which constitute the placenta, from naive PSC-derived trophectoderm. Thus, naive human PSCs, are possibly totipotent in the broad sense of the word (Io et al., Cell Stem Cell).

Academic Significance and Societal Importance of the Research Achievements

ナイーブ型ヒト多能性幹細胞(PSC)から胎盤を構成する細胞が誘導できた。マウスと違いヒトPSCは広義の全能性を有する。またナイーブ型ヒトPSCからヒト卵割期様細胞を取り出すことにも成功しており、卵割期細胞や胚盤胞の細胞を幹細胞として解析することも可能にした。ヒト胚は倫理や質の問題があるが、樹立した幹細胞を用いてヒト胚研究を補完することが可能になり、ヒト初期発生研究の基盤として学術的意義がある。
また胎盤は妊娠を維持する上で必須の臓器である。本研究で構築したモデルは、従来の倫理的規制を遵守したまま、初期胚の研究の可能性を広げ、不妊症や、胎盤に関連した妊娠合併症の病態解明に繋がる社会的意義も有する。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (31 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 7 results) Presentation (22 results) (of which Int'l Joint Research: 10 results,  Invited: 19 results) Book (1 results)

  • [Journal Article] Induction of primordial germ cell-like cells from common marmoset embryonic stem cells by inhibition of WNT and retinoic acid signaling2023

    • Author(s)
      Shono Mayumi、Kishimoto Keiko、Hikabe Orie、Hayashi Masafumi、Semi Katsunori、Takashima Yasuhiro、Sasaki Erika、Kato Kiyoko、Hayashi Katsuhiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 3186-3186

    • DOI

      10.1038/s41598-023-29850-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] mRNA-based generation of marmoset PGCLCs capable of differentiation into gonocyte-like cells2022

    • Author(s)
      Kubiura-Ichimaru Musashi、Penfold Christopher、Kojima Kazuaki、Dollet Constance、Yabukami Haruka、Semi Katsunori、Takashima Yasuhiro、Boroviak Thorsten、Kawaji Hideya、Woltjen Knut、Minoda Aki、Sasaki Erika、Watanabe Toshiaki
    • Journal Title

      BioRxiv

      Volume: N/A

    • DOI

      10.1101/2022.09.20.508677

    • Related Report
      2022 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Improved Sendai viral system for reprogramming to naive pluripotency2022

    • Author(s)
      Kunitomi Akira、Hirohata Ryoko、Arreola Vanessa、Osawa Mitsujiro、Kato Tomoaki M.、Nomura Masaki、Kawaguchi Jitsutaro、Hara Hiroto、Kusano Kohji、Takashima Yasuhiro、Takahashi Kazutoshi、Fukuda Keiichi、Takasu Naoko、Yamanaka Shinya
    • Journal Title

      Cell Reports Methods

      Volume: 2 Issue: 11 Pages: 100317-100317

    • DOI

      10.1016/j.crmeth.2022.100317

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploring the human extraembryonic mesoderm using naive pluripotent stem cells2022

    • Author(s)
      Okubo Takumi、Takashima Yasuhiro
    • Journal Title

      Cell Stem Cell

      Volume: 29 Issue: 9 Pages: 1290-1291

    • DOI

      10.1016/j.stem.2022.08.005

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Optimized protocol for naive human pluripotent stem cell-derived trophoblast induction2021

    • Author(s)
      Io Shingo、Iemura Yoshiki、Takashima Yasuhiro
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 4 Pages: 100921-100921

    • DOI

      10.1016/j.xpro.2021.100921

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of novel common marmoset embryonic stem cell lines under various conditions2021

    • Author(s)
      Keiko Kishimoto, Akiko Shimada, Haruka Shinohara, Tsukasa Takahashi, Yuko Yamada, Yuichiro Higuchi, Nao Yoneda, Hiroshi Suemizu, Kenji Kawai, Yoko Kurotaki, Kisaburo Hanazawa, Yasuhiro Takashima, Erika Sasaki
    • Journal Title

      Stem Cell Research

      Volume: 53 Pages: 102252-102252

    • DOI

      10.1016/j.scr.2021.102252

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency2021

    • Author(s)
      Takahashi Kazutoshi、Nakamura Michiko、Okubo Chikako、Kliesmete Zane、Ohnuki Mari、Narita Megumi、Watanabe Akira、Ueda Mai、Takashima Yasuhiro、Hellmann Ines、Yamanaka Shinya
    • Journal Title

      PLOS Genetics

      Volume: 17 Issue: 5 Pages: 1009587-1009587

    • DOI

      10.1371/journal.pgen.1009587

    • Related Report
      2021 Research-status 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
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒト多能性幹細胞に関する研究2022

    • Author(s)
      高島 康弘
    • Organizer
      山梨大学発生工学技術開発・実践特別教育プログラム共催(第63回セミナー)
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 次世代iPS細胞の可能性とヒト胚モデル2022

    • Author(s)
      高島 康弘
    • Organizer
      大学発シーズマッチングセミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Modeling in vitro embryonic development using naive pluripotent stem cells2022

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      Living Systems Institute Seminar, University of Exeter
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞を利用したヒト初期発生学の創出2022

    • Author(s)
      高島 康弘
    • Organizer
      再生ELSI研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Modelling peri-implantation development using na?ve human pluripotent stem cells2022

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      Cold Spring Harbor Asia
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト多能性幹細胞を用いた疑似胚盤胞に関する研究の現状と展望2022

    • Author(s)
      高島 康弘
    • Organizer
      内閣府 科学技術・イノベーション推進会議 第132回生命倫理専門調査会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の誕生・現在・未来2022

    • Author(s)
      高島 康弘
    • Organizer
      大阪府高齢者大学校
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Modelling peri-implantation development using na?ve pluripotent stem cells2022

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      第19回幹細胞シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Modeling in vitro embryonic development using naive human pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Modeling in vitro embryonic development using naive human pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      ?SY-STEM
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ナイーブ型多能性幹細胞に関する成果と可能性2021

    • Author(s)
      高島 康弘
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ナイーブ型多能性幹細胞の維持培養法2021

    • Author(s)
      高島 康弘
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Modeling in vitro embryonic development using naive pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      CiRA Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Studying primate early development using na?ve pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      第11回日本マーモセット研究会大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Modeling in vitro embryonic development using naive pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Analyzing human peri-implantation development using na?ve pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      ASHBi Symposium 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysing human peri-implantation development using in vitro models by na?ve pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      Placental Biology Course University of Cambridge
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトのいのちとからだを人為的に作る研究の進展とその倫理的問題2021

    • Author(s)
      高島 康弘
    • Organizer
      ゲノム問題検討会議
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] iPS細胞の誕生とこれから2021

    • Author(s)
      高島 康弘
    • Organizer
      大阪府高齢者大学校
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Modeling in vitro embryonic development using naive pluripotent stem cells2021

    • Author(s)
      Yasuhiro Takashima
    • Organizer
      Epigenetics in Early Mammalian Development
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトにおいて、N-cadherinは原始内胚葉の接着に必要である2021

    • Author(s)
      松藤 未夏, 大久保 巧, 高島 康弘
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Naive型ヒト多能性幹細胞の網羅的解析とFeeder free化への挑戦2021

    • Author(s)
      望月 俊吾, 遠山 周吾, 菱木 貴子, 岩崎 未央, 高島 康弘
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Book] 実験医学2021年11月号2021

    • Author(s)
      髙里 実
    • Total Pages
      129
    • Publisher
      羊土社
    • ISBN
      9784758125499
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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