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Reconstitution in culture of germ cell differentiation in mice

Planned Research

Project AreaMechanisms regulating gamete formation in animals
Project/Area Number 25114006
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

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

Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥98,670,000 (Direct Cost: ¥75,900,000、Indirect Cost: ¥22,770,000)
Fiscal Year 2017: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2016: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2015: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2014: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2013: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Keywords多能性幹細胞 / 卵母細胞 / ES/iPS細胞 / 原始卵胞 / 発生・分化 / 細胞・組織 / 始原生殖細胞 / 配偶子形成 / 体外培養 / 卵子
Outline of Final Research Achievements

The female germline undergoes a unique sequence of differentiation processes that endows totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here, this study achieved successful reconstitution in vitro of the entire process of oogenesis from pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells as well as induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the in vitro-generated eggs, thereby reconstituting a female germline cycle in a dish. This culture system will provide a unique platform for elucidating the molecular mechanisms underlying totipotency and clues to the production of oocytes of other mammalian species in culture.

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (60 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 6 results) Presentation (43 results) (of which Int'l Joint Research: 18 results,  Invited: 43 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results) Funded Workshop (1 results)

  • [Int'l Joint Research] ドイツ・ライボビッツ野生動物保護研究所/マックスデュルブリック医学研究所(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Max Delbruck Ctr. for Molecular Medicine(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [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] 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] 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] Reconstitution in vitro of the entire cycle of the mouse female germ line.2016

    • Author(s)
      Hikabe O, Hamazaki N, Nagamatsu G, Obata Y, Hirao Y, Hamada N, Shimamoto S, Imamura T, Nakashima K, Saitou M, Hayashi K
    • Journal Title

      Nature

      Volume: 539 Issue: 7628 Pages: 299-303

    • DOI

      10.1038/nature20104

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Production of functional oocytes from mouse pluripotent stem cells.2016

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

      Protocol Exchange.

      Volume: -

    • DOI

      10.1038/protex.2016.065

    • Related Report
      2016 Annual Research Report
    • Open Access
  • [Journal Article] Global Landscape and Regulatory Principles of DNA Methylation Reprogramming for Germ Cell Specification by Mouse Pluripotent Stem Cells.2016

    • Author(s)
      Shirane K, Kurimoto K, Yabuta Y, Yamaji M, Satoh J, Ito S, Watanabe A, Hayashi K, Saitou M, Sasaki H.
    • Journal Title

      Dev Cell

      Volume: 39 Pages: 87-103

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complete in vitro generation of fertile oocytes from mouse primordial germ cells2016

    • Author(s)
      Morohaku K, Tanimoto R, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, Obata Y
    • Journal Title

      Proc Natl Acad Sci USA.

      Volume: 113 Pages: 9021-9026

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rewinding the process of mammalian extinction.2016

    • Author(s)
      Saragusty J, Diecke S, Drukker M, Durrant B, Friedrich B-N I, Galli C, Göritz F, Hayashi K, Hermes R, Holtze S, Johnson S, Lazzari G, Loi P, Loring JF, Okita K, Renfree MB, Seet S, Voracek T, Stejskal J, Ryder OA, Hildebrandt TB.
    • Journal Title

      Zoo Biol.

      Volume: 35 Issue: 4 Pages: 280-292

    • DOI

      10.1002/zoo.21284

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells2015

    • Author(s)
      Kurimoto, K., Yabuta, Y., Hayashi, K., Ohta, H., Kiyonari, H., Mitani, T., Moritoki, Y., Kohri, K., Kimura, H., Yamamoto, T., Katou, Y., Shirahige, K., Saitou, M.
    • Journal Title

      Cell Stem Cell

      Volume: 16 Issue: 5 Pages: 517-532

    • DOI

      10.1016/j.stem.2015.03.002

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Possibilities in Germ Cell Research: An Engineering Insight.2015

    • Author(s)
      Esfandiari F, Mashinchian O, Ashtiani MK, Ghanian MH, Hayashi K, Saei AA, Mahmoudi M, Baharvand H.
    • Journal Title

      Trends in Biotechnology

      Volume: 33 Issue: 12 Pages: 735-746

    • DOI

      10.1016/j.tibtech.2015.09.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hayashi K, Saitou M.2014

    • Author(s)
      Perspectives of germ cell development in vitro in mammals.
    • Journal Title

      Animal Science Journal

      Volume: 85(6) Issue: 6 Pages: 617-626

    • DOI

      10.1111/asj.12199

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Perspectives of germ cell development in vitro in mammals.2014

    • Author(s)
      Hayashi K1, Saitou M.
    • Journal Title

      Animal Science Journal

      Volume: 85(6) Pages: 617-626

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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] 試験管内で機能的な生殖細胞をつくる~試験管内で世代交代はできるのか?~2017

    • Author(s)
      林克彦
    • Organizer
      日本動物学会第69回関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 生殖細胞系列の体外再構築とその利用について2017

    • Author(s)
      林克彦
    • Organizer
      関西生殖医学集談会
    • Place of Presentation
      大阪
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] A model of functional egg production in a dish2017

    • Author(s)
      Hayashi K
    • Organizer
      KOSAR
    • Place of Presentation
      Seoul
    • Year and Date
      2017-02-26
    • Related Report
      2016 Annual Research Report
    • 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 application -2017

    • 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
    • Invited
  • [Presentation] Verification of Artificial Oocytes from Stem Cells2017

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Gordon Research Conference
    • Related Report
      2017 Annual Research Report
    • 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
  • [Presentation] マウス多能性幹細胞を用いた体外培養による卵子形成過程の再構築2016

    • Author(s)
      林克彦
    • Organizer
      第29回日本動物実験代替法学会
    • Place of Presentation
      福岡
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 人工配偶子の作製技術の最前線2016

    • Author(s)
      林克彦
    • Organizer
      日本IVF学会
    • Place of Presentation
      神戸
    • Year and Date
      2016-10-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] マウスの卵母細胞系列の再構築系とその応用2016

    • Author(s)
      林克彦
    • Organizer
      第88回日本遺伝学会
    • Place of Presentation
      三島
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Artificial gametes derived from pluripotent stem cells.2016

    • Author(s)
      Hayashi K
    • Organizer
      AAAP Animal Science Congress
    • Place of Presentation
      Fukuoka
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生殖細胞系列分化培養系におけるサイトメトリー技術の適用2016

    • Author(s)
      林克彦
    • Organizer
      第26回日本サイトメトリー学会
    • Place of Presentation
      福岡
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Derivation of Germ Cells from Stem Cells.2016

    • Author(s)
      Hayashi K
    • Organizer
      IFFS2016
    • Place of Presentation
      Delhi, India
    • Year and Date
      2016-06-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Artificial oocyte production from pluripotent stem cells in mice.2016

    • Author(s)
      Hayashi K
    • Organizer
      Epigenetic Penetrance of Reproductive Technologies
    • Place of Presentation
      Teramo, Italy
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 培養皿上で受精可能な卵子をつくる~基礎と応用に向けて~2016

    • Author(s)
      林克彦
    • Organizer
      日本生殖再生医学会
    • Place of Presentation
      シェーンバッハ・サボー(東京)
    • Year and Date
      2016-03-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 試験管内生殖細胞の最前線と課題2016

    • Author(s)
      林克彦
    • Organizer
      日本生殖内分泌学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2016-01-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Reconstitution of mouse oogenesis in vitro2015

    • Author(s)
      林克彦
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Derivation of Germ Cells from Stem Cells2015

    • Author(s)
      HAYASHI, Katsuhiko
    • Organizer
      World Congress on In Vitro Fertilization
    • Place of Presentation
      Tivoli Congress Center, Copenhagen
    • Year and Date
      2015-09-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 人工配偶子の最前線と課題2015

    • Author(s)
      林克彦
    • Organizer
      日本IVF学会
    • Place of Presentation
      アクロス福岡
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 雄から卵子?:体外卵子産生系で見えてくるもの2015

    • Author(s)
      林克彦
    • Organizer
      日本動物学会
    • Place of Presentation
      朱鷺メッセ
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 雌性生殖細胞系列サイクルの試験管内再構成2015

    • Author(s)
      林克彦
    • Organizer
      日本繁殖生物学会
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Reconstitution of the Female Germline in a Dish2015

    • Author(s)
      HAYASHI, Katsuhiko
    • Organizer
      Gordon Research Conference (Fertilization & Activation of Development)
    • Place of Presentation
      Holderness School
    • Year and Date
      2015-07-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多能性幹細胞から生殖細胞への分化誘導2015

    • Author(s)
      林克彦
    • Organizer
      生殖医療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Artificial Gameteの現状と今後の展望~技術開発とその意義~2015

    • Author(s)
      林克彦
    • Organizer
      日本医学会総会2015関西
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Propagating generations of healthy mice using manufactured oocytes2015

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Ovarian Club V
    • Place of Presentation
      香港
    • Year and Date
      2015-01-31 – 2015-02-02
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Propagating generation of healthy mice using manifactured oocytes2015

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Ovarian Club V
    • Place of Presentation
      香港
    • Year and Date
      2015-01-31
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of eggs from mouse embryonic stem cells2014

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Society of Reproduction and Fertility
    • Place of Presentation
      エジンバラ(英国)
    • Year and Date
      2014-09-21
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of eggs from mouse embryonic stem cells2014

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      Society of Reproduction and Fertility
    • Place of Presentation
      英国
    • Year and Date
      2014-09-21
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] In vitro germline formation from pluripotent stem cells2014

    • Author(s)
      林克彦
    • Organizer
      第47回日本発生生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27 – 2014-05-30
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] in vitro gemline formation from pluripotent stem cells2014

    • Author(s)
      林克彦
    • Organizer
      第47回日本発生生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Prospects of gamete production from pluripotent stem cells2014

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      The 45th meeting of the Dutch Society of Obstetrics and Gynaecology
    • Place of Presentation
      オランダ
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Making Oocytes and Babies from Stem Cells2014

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      The Congress of the Asia Pacific Initiative on Reproduction
    • Place of Presentation
      オーストラリア
    • Year and Date
      2014-04-04 – 2014-04-06
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Making Oocytes abd Babies from Stem Cells2014

    • Author(s)
      Katsuhiko Hayashi
    • Organizer
      The Congress of the Asia Pacific Initiative on Reproduction
    • Place of Presentation
      ブリスベン(オーストラリア)
    • Year and Date
      2014-04-04
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 始原生殖細胞を機能的に成熟した卵母細胞へと分化させる培養方法2016

    • Inventor(s)
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Holder
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 始原生殖細胞を機能的に成熟した卵母細胞へと分化させる培養方法2015

    • Inventor(s)
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Holder
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Funded Workshop] The International Research Symposium on Regulation of Germ Cell Development in vivo and in vitro2017

    • Related Report
      2017 Annual Research Report

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Published: 2013-07-10   Modified: 2019-03-29  

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