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Analysis of early post-implantation development and establishment of physiological ex vivo culture method in primate

Planned Research

Project AreaA new foundation for primate developmental biology
Project/Area Number 20H05761
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionKyoto University

Principal Investigator

Nakamura Tomonori  京都大学, 白眉センター, 特定准教授 (90648429)

Co-Investigator(Kenkyū-buntansha) 岡本 郁弘  京都大学, 高等研究院, 特定講師 (40648424)
Project Period (FY) 2020-10-02 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000)
Fiscal Year 2022: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2021: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2020: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywords霊長類 / 発生学 / scRNA-seq / 着床後胚発生 / 次元の呪い / カニクイザル
Outline of Research at the Start

本研究計画A01では、研究領域の目標である非ヒト霊長類を用いた着床後胚の発生学研究基盤構築のうち、霊長類着床後胚発生研究が滞っていた大きな原因の一つである試料採取の困難性に対する回避策の提供を目標とする。このため、着床期のカニクイザル胚に出現する全細胞種をscRNA-seqにより同定し、同時に主要マーカー遺伝子の発現部位を明らかにすることで、位置情報を保持した遺伝子発現動態の完全解明を目指す。また生存率の極めて低い既存のEx vivo culture法を改良し、子宮内で発生する胚周囲の環境を参考に生存率向上を目指す。そしてA02で再現される子宮内膜環境への着床モデル構築を目指す。

Outline of Final Research Achievements

In this research project, we focused on primate-specific developmental phenomena immediately after implantation using cynomolgus macaques. First, we performed scRNA-seq on embryos at E15-E23 to identify all cell types emerging during early post-implantation. To this end, we developed an algorithm, RECODE, to solve the "curse of dimensionality" problem inherent in scRNA-seq. We found that the developmental stages of embryos change significantly between E17 and E19, and the characters of EXMC and AmEcto, which are not present in mice of the same age. We also found that the differences of inactivation mechanisms of the X chromosome between mice and the mokyes. Furthermore, we investigated the germline lineage induction from primate ESCs and found that the lineage is via AmEcto.

Academic Significance and Societal Importance of the Research Achievements

ヒトの流産の多くが初期に起こると言われているが、ヒトの着床直後の胚発生はなぞに包まれている。また多能性幹細胞を用いた再生医療/創薬研究も大きな期待を寄せられているが、霊長類多能性幹細胞の実態は未知な部分が多い。本研究成果は、大きな期待を寄せられている今後のヒト胚発生研究や臨床応用研究、さらには多能性幹細胞研究のための重要な参照データとなり、今後の研究発展を支える基盤となるものである。

Report

(2 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • Research Products

    (8 results)

All 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program2021

    • Author(s)
      Kojima Yoji、Yamashiro Chika、Murase Yusuke、Yabuta Yukihiro、Okamoto Ikuhiro、Iwatani Chizuru、Tsuchiya Hideaki、Nakaya Masataka、Tsukiyama Tomoyuki、Nakamura Tomonori、Yamamoto Takuya、Saitou Mitinori
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 5 Pages: 202000974-202000974

    • DOI

      10.26508/lsa.202000974

    • NAID

      120006979739

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] Cyclosporin A and FGF signaling support the proliferation/survival of mouse primordial germ cell-like cells in vitro†2020

    • Author(s)
      Ohta Hiroshi、Yabuta Yukihiro、Kurimoto Kazuki、Nakamura Tomonori、Murase Yusuke、Yamamoto Takuya、Saitou Mitinori
    • Journal Title

      Biology of Reproduction

      Volume: 104 Issue: 2 Pages: 344-360

    • DOI

      10.1093/biolre/ioaa195

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ZGLP1 is a determinant for the oogenic fate in mice2020

    • Author(s)
      Nagaoka So I.、Nakaki Fumio、Miyauchi Hidetaka、Nosaka Yoshiaki、Ohta Hiroshi、Yabuta Yukihiro、Kurimoto Kazuki、Hayashi Katsuhiko、Nakamura Tomonori、Yamamoto Takuya、Saitou Mitinori
    • Journal Title

      Science

      Volume: 367 Issue: 6482 Pages: 4115-4115

    • DOI

      10.1126/science.aaw4115

    • NAID

      120006850276

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Long‐term expansion with germline potential of human primordial germ cell‐like cells in?vitro2020

    • Author(s)
      Murase Yusuke、Yabuta Yukihiro、Ohta Hiroshi、Yamashiro Chika、Nakamura Tomonori、Yamamoto Takuya、Saitou Mitinori
    • Journal Title

      The EMBO Journal

      Volume: 39 Issue: 21 Pages: 104929-104929

    • DOI

      10.15252/embj.2020104929

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 霊長類特異的多能性状態の解明2020

    • Author(s)
      Tomonori Nakamura* , Yusuke Imoto, Yasuaki Hiraoka, Mitinori Saitou
    • Organizer
      第53回発生生物学会年会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identifying cells hidden by curse of dimensionality2020

    • Author(s)
      Tomonori Nakamura
    • Organizer
      The 1st ASHBi SignAC international workshop 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 観測ノイズ削減法の開発2020

    • Inventor(s)
      井元祐介、中村友紀、平岡裕章、斎藤通紀
    • Industrial Property Rights Holder
      井元祐介、中村友紀、平岡裕章、斎藤通紀
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2020-10-30   Modified: 2024-01-30  

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