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Reconstitution of common marmoset oogenesis from pluripotent stem cells

Research Project

Project/Area Number 17H01395
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

Hayashi Katsuhiko  九州大学, 医学研究院, 教授 (20287486)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2019: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2018: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2017: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords多能性幹細胞 / コモンマーモセット / 卵母細胞 / 始原生殖細胞 / 生殖巣体細胞 / マーモセットES細胞 / 再生医学 / 応用動物
Outline of Final Research Achievements

We established a culture system to induce primordial germ cell-like cells (cj-PGCLCs) from common marmoset ES cells. The transcriptomic and epigenetic features of cj-PGCLCs were quite similar to those of human PGCLCs. Based on the transcriptome analysis, we identified surface marker antigens that are specifically expressed on cj-PGCLCs. By recognizing these antigens with antibodies, we were able to isolate cj-PGCLCs from a variety of common marmoset ES cell lines. The obtained cj-PGCLCs were differentiated into the late germ cell lineage by co-culture with mouse embryonic ovarian somatic cells, suggesting that they have the ability to differentiate into gametes.

Academic Significance and Societal Importance of the Research Achievements

精子や卵子に至る生殖細胞系列の形成過程の解明は生物学的および医学的に極めて大きい意義をもつが、解析のために利用できる生体内(胎仔内)の生殖細胞系列は量的および質的に不足している。本研究により、ヒトに近いコモンマーモセットのES細胞から始原生殖細胞を分化誘導する培養系を確立したことにより、その発生過程における機能的な遺伝子の同定などが飛躍的に進むことが期待される。これらの機能的な遺伝子はヒトにおいても保存されていると考えられることから、本研究の成果はヒトの不妊原因や発生異常の原因究明に貢献すると考えられる。

Report

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

    (58 results)

All 2021 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 9 results) Presentation (44 results) (of which Int'l Joint Research: 25 results,  Invited: 41 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Artificially produced gametes in mice, humans and other species2021

    • Author(s)
      Hayashi Katsuhiko、Galli Cesare、Diecke Sebastian、Hildebrandt Thomas B.
    • Journal Title

      Reproduction, Fertility and Development

      Volume: 33 Issue: 2 Pages: 91-91

    • DOI

      10.1071/rd20265

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Environmental factors for establishment of the dormant state in oocytes2020

    • Author(s)
      Hayashi Katsuhiko、Shimamoto So、Nagamatsu Go
    • Journal Title

      Development, Growth & Differentiation

      Volume: 62 Issue: 3 Pages: 150-157

    • DOI

      10.1111/dgd.12653

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice.2020

    • Author(s)
      Hamada N, Hamazaki N, Shimamoto S, Hikabe O, Nagamatsu G, Takada Y, Kato K, Hayashi K.
    • Journal Title

      PLoS Genetics

      Volume: 16 Issue: 3 Pages: e1008676-e1008676

    • DOI

      10.1371/journal.pgen.1008676

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes.2019

    • Author(s)
      Nagamatsu G, Shimamoto S, Hamazaki N, Nishimura Y, Hayashi K.
    • Journal Title

      Science Advances

      Volume: 5 Issue: 6

    • DOI

      10.1126/sciadv.aav9960

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia induces the dormant state in oocytes through expression of Foxo3.2019

    • Author(s)
      Shimamoto S, Nishimura Y, Nagamatsu G, Hamada N, Kita H, Hikabe O, Hamazaki N, Hayashi K.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: 116 Issue: 25 Pages: 12321-12326

    • DOI

      10.1073/pnas.1817223116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro reconstitution of germ cell development†2019

    • Author(s)
      Hayashi Katsuhiko
    • Journal Title

      Biology of Reproduction

      Volume: 101 Issue: 3 Pages: 567-578

    • DOI

      10.1093/biolre/ioz111

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem Cell-Derived Human Gametes: The Public Engagement Imperative.2019

    • Author(s)
      Adashi EY, Cohen IG, Hanna JH, Surani AM, Hayashi K.
    • Journal Title

      Trends Mol Med.

      Volume: 25 Issue: 3 Pages: 165-167

    • DOI

      10.1016/j.molmed.2019.01.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Embryos and embryonic stem cells from the white rhinoceros.2018

    • Author(s)
      Hildebrandt TB, Hermes R, Colleoni S, Diecke S, Holtze S, Renfree MB, Stejskal J, Hayashi K, Drukker M, Loi P, Groitz F, Lazzari G, Galli C.
    • Journal Title

      Nat Commun.

      Volume: 9 Issue: 1 Pages: 2589-2589

    • DOI

      10.1038/s41467-018-04959-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stem cells, in vitro gametogenesis and male fertility2017

    • Author(s)
      Nagamatsu Go、Hayashi Katsuhiko
    • Journal Title

      Reproduction

      Volume: 154 Issue: 6 Pages: F79-F91

    • DOI

      10.1530/rep-17-0510

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone morphogenetic protein and retinoic acid synergistically specify female germ‐cell fate in mice2017

    • Author(s)
      Miyauchi Hidetaka、Ohta Hiroshi、Nagaoka So、Nakaki Fumio、Sasaki Kotaro、Hayashi Katsuhiko、Yabuta Yukihiro、Nakamura Tomonori、Yamamoto Takuya、Saitou Mitinori
    • Journal Title

      The EMBO Journal

      Volume: 36 Issue: 21 Pages: 3100-3119

    • DOI

      10.15252/embj.201796875

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstitution of mouse oogenesis in a dish from pluripotent stem cells2017

    • Author(s)
      Hayashi Katsuhiko、Hikabe Orie、Obata Yayoi、Hirao Yuji
    • Journal Title

      Nature Protocols

      Volume: 12 Issue: 9 Pages: 1733-1744

    • DOI

      10.1038/nprot.2017.070

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Bidirectional Promoter-Derived lncRNAs from Small-Scale Samples Using Pre-Amplification-Free Directional RNA-seq Method2017

    • Author(s)
      Hamazaki Nobuhiko、Nakashima Kinichi、Hayashi Katsuhiko、Imamura Takuya
    • Journal Title

      Methods in Molecular Biology

      Volume: 1605 Pages: 83-103

    • DOI

      10.1007/978-1-4939-6988-3_6

    • ISBN
      9781493969869, 9781493969883
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Artificially produced gametes in mice, humans and other species2021

    • Author(s)
      HAYASHI, Katsuhiko
    • Organizer
      International Embryo Technology Society(
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Oocyte production in culture toward application to species conservation2021

    • Author(s)
      HAYASHI, Katsuhiko
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵母細胞形成における性染色体の機能2020

    • Author(s)
      林克彦
    • Organizer
      日本内分泌学会学術総
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Understanding of mammalian oogenesis by reconstitution in vitro2020

    • Author(s)
      HAYASHI, Katsuhiko
    • Organizer
      日本発生生物学会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of transcription factors orchestrating oocyte growth2020

    • Author(s)
      HAMAZAKI, Nobuhiko and HAYASHI, Katsuhiko
    • Organizer
      日本分子生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生殖細胞再生技術の最前線2020

    • Author(s)
      林克彦
    • Organizer
      日本生殖医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Basic Research:In-Vitro Oogenesis from Pluripotent Stem Cells2020

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      ASPIRE 8th Masterclass
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generating and modifying functional sperm and eggs from stem cells2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      De Snoo van ‘t Hoogerhuijs Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Stem Cells ~Regeneration of Oocytes~2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      World Congress of International Federation of Fertility
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reconstitution and Understanding of Mammalian Oogenesis2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      浙江省医学会生殖医学分会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 実験動物における生殖細胞系列再構築系の展開2019

    • Author(s)
      林克彦
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Reconstitution and understanding of mammalian oogenesis2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Stem Cell Symposium
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 原始卵胞の成立機序と人工的作製2019

    • Author(s)
      林克彦
    • Organizer
      生殖バイオロジー東京シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 卵母細胞系列の再構築系の現状と課題2019

    • Author(s)
      林克彦
    • Organizer
      千里ライフサイエンスセミナー オルガノイド研究の現状と課題
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 卵母細胞の休止状態が保たれるメカニズム2019

    • Author(s)
      林克彦
    • Organizer
      日本遺伝学会第91回大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 生殖細胞誘導システムを構築するための動物細胞を用いた前衛的研究2019

    • Author(s)
      林克彦
    • Organizer
      第22回日本IVF学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Gametes from pluripotent stem cells2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      International Scciety of In Vitro Fertilization
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵子が長生きするしくみ -マウスの知見から-2019

    • Author(s)
      林克彦
    • Organizer
      第34回日本女性医学学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Reconstitution of mammalian oogenesis using pluripotent stem cells2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      International Society of Fertility Preservation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 個体の起源とその構築2019

    • Author(s)
      林克彦
    • Organizer
      第64回日本人類遺伝学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A mechanism underlying sustainable oocyte production in mouse germ line2019

    • Author(s)
      林克彦
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A stem cell-based approach to understanding of mammalian oogenesis2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      SY-stem symposium 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reconstitution and Understanding of Mammalian Oogenesis2019

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      BDR symposium 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] An In-vitro Model System to Study and Produce Oocyte2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Asia Pacific Initiative on Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞による卵母細胞の分化過程の再構築2018

    • Author(s)
      林克彦
    • Organizer
      日本内分泌学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] in vitro gametogenesis from stem cells2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Korean Society of Reproductive Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Oocytes from stem cells and back2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      The European Society of Human Reproduction & Embryology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A mechanism ensuring a dormant state of oocytes in the ovary2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Basel Stem Cell Symposium: Stem Cell Dynamics Throughout Life
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A stem cell-based approach to reconstitution of mammalian oogenesis2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      5th Conference of Frontiers in Reproductive Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A Novel Approach to Understanding oogenesis with in vitro reconstitution system2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      EMBO symposium: Molecular Mechanisms of Developmental and Regenerative Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵母細胞分化培養系から得られる新知見2018

    • Author(s)
      林克彦
    • Organizer
      第13回生殖発生医学
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] In vitro reconstitution of oogenesis in the mouse; how to establish the culture system, mostly empirical2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Asia-Pacific Bioinformatics Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding of oogenesis by stem cell-based technologies2018

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      KEY Forum 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a Model Culture System to Produce Eggs in Vitro2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Ovarian Club X
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵母細胞の再構築系で見えてくるもの2017

    • Author(s)
      林克彦
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 卵子の再生技術から見えてくるもの2017

    • Author(s)
      林克彦
    • Organizer
      第62回日本生殖医学会学術講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Possibility of gametogenesis in vitro from stem cells; what we need for application2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      PSRM2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 皮膚からの卵子作製 ~マウス知見をもとに~2017

    • Author(s)
      林克彦
    • Organizer
      日本IVF学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Understanding of PGC-oocyte differentiation using in vitro reconstitution system2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      World Congress of Reproductive Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵母細胞の形成機構の解明と再生;体内と培養系の狭間にみえてくるもの2017

    • Author(s)
      林克彦
    • Organizer
      第35回日本受精着床学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Reconstitution As a Tool for a Better Understanding of Germ Cell Development2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Society for the Study on Reproduction
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Verification of Artificial Oocytes from Stem Cells2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Gordon Research Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] FUNCTIONAL EGGS CREATED IN A DISH FROM MOUSE PLURIPOTENT STEM CELLS2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      ISSCR
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanisms underlying differentiation from primordial germ cells to oocytes2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Japanese Society of Developmental Biologists
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Encyclopedia of Reproduction2018

    • Author(s)
      Michael K. Skinner
    • Total Pages
      3868
    • Publisher
      Academic Press Inc
    • ISBN
      9780128118993
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 始原生殖細胞をin vitroで原始卵胞に分化する方法2018

    • Inventor(s)
      永松剛、西村洋平、林克彦
    • Industrial Property Rights Holder
      永松剛、西村洋平、林克彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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