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Improvement of Somatic Cell Nuclear Transfer technology by Epigenome-editing

Research Project

Project/Area Number 16H06146
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Matoba Shogo  国立研究開発法人理化学研究所, バイオリソース研究センター, 専任研究員 (20585202)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsエピジェネティクス / 体細胞クローン / ゲノムインプリンティング / 胎盤形成 / アミノ酸輸送 / H3K9me3 / H3K27me3 / Slc38a4 / 体細胞核移植 / クローン / ヒストン修飾 / エピゲノム編集 / インプリント遺伝子 / 着床後発生 / マウス / 初期化 / 発生・分化 / 応用動物 / ゲノム / 獣医学 / 再生医学
Outline of Final Research Achievements

We performed epigenomic analysis of mouse cloned embryos to improve the efficiency and quality of somatic cell cloning by developing epigenome editing technologies. Firstly, a combination of the use of Xist KO donor cells and the removal of H3K9me3 by Kdm4d significantly improved the efficiency of mouse cloning. Next, comprehensive epigenome analyses revealed that genomic imprinting by H3K27me3 was completely lost in cloned embryos. Furthermore, we also revealed that one of the H3K27me3-imprint genes, Slc38a4, plays critical role in placental development. In summary, we successfully improved the efficiency of mouse cloning and identified candidate factors that might be responsible for placental abnormalities in clones.

Academic Significance and Societal Importance of the Research Achievements

体細胞クローン法では、ドナーとなる生物と同じゲノム情報を持ったコピー生物(クローン)を作製できるため、貴重な遺伝子資源の保存や、絶滅危惧種の維持・繁殖、さらには再生医療にも貢献する可能性のある技術ですが、非常に効率が低く、運よく生まれた個体も胎盤異常などを伴います。本研究では、マウスをモデルとしてクローンの低効率を改善することに成功し、さらに、胎盤異常の原因候補因子を発見しました。

Report

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

    (31 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (3 results) Remarks (2 results)

  • [Int'l Joint Research] ハーバード大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 浙江大学(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 浙江大学(中国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ハーバード大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Acrosin is essential for sperm penetration through the zona pellucida in hamsters2020

    • Author(s)
      Hirose Michiko、Honda Arata、Fulka Helena、Tamura-Nakano Miwa、Matoba Shogo、Tomishima Toshiko、Mochida Keiji、Hasegawa Ayumi、Nagashima Kiyoshi、Inoue Kimiko、Ohtsuka Masato、Baba Tadashi、Yanagimachi Ryuzo、Ogura Atsuo
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 5 Pages: 2513-2518

    • DOI

      10.1073/pnas.1917595117

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Paternal knockout of Slc38a4/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice2019

    • Author(s)
      Matoba Shogo、Nakamuta Shoko、Miura Kento、Hirose Michiko、Shiura Hirosuke、Kohda Takashi、Nakamuta Nobuaki、Ogura Atsuo
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 42 Pages: 21047-21053

    • DOI

      10.1073/pnas.1907884116

    • NAID

      130007719356

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Somatic Cell Nuclear Transfer in Mice: Basic Protocol and Its Modification for Correcting X Chromosome Inactivation Status2018

    • Author(s)
      Inoue Kimiko、Matoba Shogo、Ogura Atsuo
    • Journal Title

      Methods Mol Biol.

      Volume: 1861 Pages: 55-65

    • DOI

      10.1007/978-1-4939-8766-5_5

    • ISBN
      9781493987658, 9781493987665
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos2018

    • Author(s)
      Hirose Michiko、Hada Masashi、Kamimura Satoshi、Matoba Shogo、Honda Arata、Motomura Kaori、Ogonuki Narumi、Shawki Hossam H.、Inoue Kimiko、Takahashi Satoru、Ogura Atsuo
    • Journal Title

      Epigenetics

      Volume: 13 Issue: 7 Pages: 693-703

    • DOI

      10.1080/15592294.2018.1507199

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatic Cell Nuclear Transfer Reprogramming: Mechanisms and Applications2018

    • Author(s)
      Matoba Shogo、Zhang Yi
    • Journal Title

      Cell Stem Cell

      Volume: 23 Issue: 4 Pages: 471-485

    • DOI

      10.1016/j.stem.2018.06.018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development2018

    • Author(s)
      Matoba Shogo、Wang Huihan、Jiang Lan、Lu Falong、Iwabuchi Kumiko A.、Wu Xiaoji、Inoue Kimiko、Yang Lin、Press William、Lee Jeannie T.、Ogura Atsuo、Shen Li、Zhang Yi
    • Journal Title

      Cell Stem Cell

      Volume: 23 Issue: 3 Pages: 343-354

    • DOI

      10.1016/j.stem.2018.06.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reprogramming of Chromatin Accessibility in Somatic Cell Nuclear Transfer Is DNA Replication Independent2018

    • Author(s)
      Djekidel Mohamed Nadhir、Inoue Azusa、Matoba Shogo、Suzuki Tsukasa、Zhang Chunxia、Lu Falong、Jiang Lan、Zhang Yi
    • Journal Title

      Cell Reports

      Volume: 23 Issue: 7 Pages: 1939-1947

    • DOI

      10.1016/j.celrep.2018.04.036

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Application of auxin-inducible degron technology to mouse oocyte activation with PLCζ2018

    • Author(s)
      1.Miura K, Matoba S, Ogonuki N, Namiki T, Ito J, Kashiwazaki N, Ogura A
    • Journal Title

      Journal of Reproduction and Development

      Volume: 64 Issue: 4 Pages: 319-326

    • DOI

      10.1262/jrd.2018-053

    • NAID

      130007437366

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common marmoset (Callithrix jacchus).2018

    • Author(s)
      Ogonuki N, Inoue H, Matoba S, Kurotaki YK, Kassai H, Abe Y, Sasaki E, Aiba A, Ogura A
    • Journal Title

      Mol Reprod Dev

      Volume: - Issue: 5 Pages: 376-386

    • DOI

      10.1002/mrd.22971

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo genetic manipulateon of spermatogonial stem cells and their microenvironment by adeno-associated viruses.2018

    • Author(s)
      Watanabe S., Kanatsu-Shinohara, M., Ogonuki N., Matoba S., Ogura A., Shinohara T.
    • Journal Title

      Stem Cell Reports

      Volume: S2213-6711 (18) Issue: 5 Pages: 30132-2

    • DOI

      10.1016/j.stemcr.2018.03.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transfer of a mouse artificial chromosome into spermatogonial stem cells genetates transchromosomic mice,2017

    • Author(s)
      Shinohara T, Kazuki K, Ogonuki N, Morimoto H, Matoba S, Hiramatsu K, Honma K, Suzuki T, Hara T, Ogura A, Oshimura M, Kanatsu-Shinohara M, Kazuki Y.
    • Journal Title

      Stem Cell Reports.

      Volume: 9(4) Issue: 4 Pages: 1180-1191

    • DOI

      10.1016/j.stemcr.2017.08.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene2017

    • Author(s)
      Michiko Hirose, Ayumi Hasegawa, Keiji Mochida, Shogo Matoba, Yuki Hatanaka, Kimiko Inoue, Tatsuhiko Goto, Hideki Kaneda, Ikuko Yamada, Tamio Furuse, Kuniya Abe, Yoshihisa Uenoyama, Hiroko Tsukamura, Shigeharu Wakana, Arata Honda, and Atsuo Ogura
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 42476-42476

    • DOI

      10.1038/srep42476

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adeno-associated virus-mediated delivery of genes into mouse spermatogonial stem cells.2017

    • Author(s)
      Watanabe, S., Kanatsu-Shinohara, M., Ogonuki, N., Matoba, S., Ogura, A., and Shinohara, T.
    • Journal Title

      Biol. Reprod.

      Volume: 96 Pages: 221-231

    • DOI

      10.1095/biolreprod.116.143495

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mouse D1Pas1, a DEAD-box RNA helicase, is required for the completion of first meiotic prophase in male germ cells2016

    • Author(s)
      Inoue H, Ogonuki N, Hirose M, Hatanaka Y, Matoba S, Chuma S, Kobayashi K, Wakana S, Noguchi J, Inoue K, Tanemura K, *Ogura A
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 478 Issue: 2 Pages: 592-8

    • DOI

      10.1016/j.bbrc.2016.07.109

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 胎盤に発現するアミノ酸トランスポーター遺伝子Slc38a4のノックアウトマウス胚は胎盤低形成および胎児発育不全を示す2019

    • Author(s)
      的場章悟、中牟田祥子、三浦健人、広瀬美智子、中牟田信明、小倉淳郎
    • Organizer
      第112会日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウスY染色体上遺伝子ノックアウトによる性スペクトラム表現型への影響2019

    • Author(s)
      的場章悟、三浦健人、尾崎藍、小倉淳郎、田村勝
    • Organizer
      第162回日本獣医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス体細胞クローン胚ではヒストン修飾H3K27me3によるゲノムインプリンティングが破綻している2018

    • Author(s)
      的場章悟, Li Shen, 井上貴美子, 小倉淳郎, Yi Zhang
    • Organizer
      第111回日本繁殖生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of histone modifications on epigenetic reprogramming by somatic cell nuclear transfer2018

    • Author(s)
      的場章悟
    • Organizer
      第90回日本遺伝学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Genome-wide analysis reveals incomplete reprogramming of DNA methylation in blastocysts created by somatic cell nuclear transfer2017

    • Author(s)
      的場章悟, Shen L, 小倉淳郎, Zhang Y
    • Organizer
      RIKEN Epigenetics in Tsukuba
    • Place of Presentation
      理化学研究所バイオリソースセンター(茨城県つくば市)
    • Year and Date
      2017-02-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Slc38a4/SNAT4, a system A amino acid transporter, plays critical roles for mouse placental development.2017

    • Author(s)
      Matoba Shogo, Ogura Atsuo
    • Organizer
      Fourth World Congress of Reproductive Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 体細胞クローン胚のDNAメチローム解析によって見える全能性獲得過程とその異常2017

    • Author(s)
      的場章悟, Li Shen, 小倉淳郎, Yi Zhang
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 体細胞クローン胚のDNAメチローム解析による初期化異常パターンの同定2016

    • Author(s)
      的場章悟, Shen L, 小倉淳郎, Zhang Y
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Related Report
      2016 Annual Research Report
  • [Book] 体細胞クローン胚においてはヒストンのメチル化によるインプリント制御が破綻している2018

    • Author(s)
      的場章悟, Yi Zhang
    • Total Pages
      4
    • Publisher
      ライフサイエンス 新着論文レビュー
    • Related Report
      2018 Annual Research Report
  • [Book] クローン胚ではヒストンのメチル化依存的なゲノムインプリンテイングが破綻している2018

    • Author(s)
      的場章悟
    • Total Pages
      4
    • Publisher
      羊土社 実験医学2018年12月号
    • ISBN
      9784758125147
    • Related Report
      2018 Annual Research Report
  • [Book] マウス表現型解析スタンダード 実験医学別冊 「顕微授精・核移植クローン技術:配偶子・体細胞からの産仔作出」2016

    • Author(s)
      小倉淳郎, 的場章悟
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      https://www.riken.jp/press/2019/20191008_3/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 理研バイオリソースセンター 遺伝工学基盤技術室

    • URL

      http://ja.brc.riken.jp/lab/kougaku/index.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2022-01-31  

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