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Understanding of totipotency through characterization of interactions between transposable elements and early embryos

Planned Research

Project AreaProgram of totipotency: From decoding to designing
Project/Area Number 19H05753
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 InstitutionKeio University

Principal Investigator

Siomi Haruhiko  慶應義塾大学, 医学部(信濃町), 教授 (60202107)

Project Period (FY) 2019-06-28 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥104,780,000 (Direct Cost: ¥80,600,000、Indirect Cost: ¥24,180,000)
Fiscal Year 2023: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2022: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2021: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2020: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2019: ¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
KeywordsPIWI / piRNA / ハムスター / トランスポゾン / 初期胚発生 / ZGA / 転移因子 / 着床前胚 / 全能性 / 多能性 / 初期胚 / エピゲノム
Outline of Research at the Start

本研究の概要は、これまで得られた情報と開発した解析技術をもとに、転移因子(トランスポゾン)が哺乳類の全能性プログラムに寄与する可能性を検証するための研究である。

Outline of Final Research Achievements

Result 1: Many animals have a conserved adaptive genome defence system known as the Piwi-interacting RNA (piRNA) pathway, which is essential for germ cell development and function. Disruption of individual mouse Piwi genes results in male but not female sterility, leading to the assumption that PIWI genes play little or no role in mammalian oocytes. With an improved high-quality genome assembly and annotation of golden hamster, we were able to generate PIWI-defective golden hamsters, which have defects in the production of functional oocytes.
Result 2: Zygotic genome activation (ZGA) is a critical step that promotes totipotency. MERVL is transiently upregulated during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remained elusive. We were able to demonstrate that MERVL expression is essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development.

Academic Significance and Societal Importance of the Research Achievements

ハムスターをモデル動物として使用するための基盤整備を行い、PIWI遺伝子の変異がメスの不妊につながることを世界ではじめて証明した。これはヒト女性の不妊の原因としてPIWI遺伝子の変異がゲノム解析の対象となるきっかけとなった。
一方、以前より哺乳類初期杯においてトランスポゾンが高発現することが知られていたがその機能は不明であった。私達は多コピー遺伝因子の発現を抑制する手法を開発し、マウス初期杯において高発現するトランスポゾンMERVLを抑制したところ、胚発生が停止した。これは着床前胚においてトランスポゾンの発現が胚発生に不可欠であることを示した世界で初めての例となった。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (44 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 15 results) Presentation (25 results) (of which Int'l Joint Research: 13 results,  Invited: 23 results) Remarks (2 results)

  • [Int'l Joint Research] University of Pennsylvania(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Retrotransposon renaissance in early embryos2024

    • Author(s)
      Guo Y, Li TD, Modzelewski AJ, Siomi H.
    • Journal Title

      Trends in Genetics

      Volume: 40 Issue: 1 Pages: 39-51

    • DOI

      10.1016/j.tig.2023.10.010

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcription of MERVL retrotransposons is required for preimplantation embryo development2023

    • Author(s)
      Sakashita Akihiko、Kitano Tomohiro、Ishizu Hirotsugu、Guo Youjia、Masuda Harumi、Ariura Masaru、Murano Kensaku、Siomi Haruhiko
    • Journal Title

      Nature Genetics

      Volume: 55 Issue: 3 Pages: 484-495

    • DOI

      10.1038/s41588-023-01324-y

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mod(mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers2022

    • Author(s)
      Chikara Takeuchi, Moe Yokoshi, Shu Kondo, Aoi Shibuya, Kuniaki Saito, Takashi Fukaya, Haruhiko Siomi, Yuka W Iwasaki
    • Journal Title

      Nucleic Acids Research

      Volume: 50 Issue: 20 Pages: 11580-11599

    • DOI

      10.1093/nar/gkac1034

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TDP-43 safeguards the embryo genome from L1 retrotransposition2022

    • Author(s)
      Li Ten D.、Murano Kensaku、Kitano Tomohiro、Guo Youjia、Negishi Lumi、Siomi Haruhiko
    • Journal Title

      Science Advances

      Volume: 8 Issue: 47

    • DOI

      10.1126/sciadv.abq3806

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant2022

    • Author(s)
      Mise-Omata, S., M. Ikeda, M. Takeshita, Y. Uwamino, M. Wakui, T. Arai, A. Yoshifuji, K. Murano, H. Siomi, K. Nakagawara, M. Ohyagi, M. Ando, N. Hasegawa, H. Saya, M. Murata, K. Fukunaga, H. Namkoong, X. Lu, S. Yamasaki, and A. Yoshimura.
    • Journal Title

      J Immunol

      Volume: 209 Issue: 11 Pages: 2104-2113

    • DOI

      10.4049/jimmunol.2200525

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pro108Ser mutation of SARS-CoV-2 3CLpro reduces the enzyme activity and ameliorates the clinical severity of COVID-192022

    • Author(s)
      Abe K, Kabe Y, Uchiyama S, Iwasaki YW, Ishizu H, Uwamino Y, Takenouchi T, Uno S, Ishii M, Maruno T, Noda M, Murata M, Hasegawa N, Saya H, Kitagawa Y, Fukunaga K, Amagai M, Siomi H, Suematsu M, Kosaki K, Keio Donner Project.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 1299-1299

    • DOI

      10.1038/s41598-022-05424-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines2021

    • Author(s)
      Murano K, Guo Y, Siomi H.
    • Journal Title

      Biochem Soc Trans

      Volume: 49(6) Issue: 6 Pages: 2879-2890

    • DOI

      10.1042/bst20210859

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of functional oocytes requires maternally expressed PIWI genes and piRNAs in golden hamsters2021

    • Author(s)
      Hasuwa Hidetoshi、Iwasaki Yuka W.、Au Yeung Wan Kin、Ishino Kyoko、Masuda Harumi、Sasaki Hiroyuki、Siomi Haruhiko
    • Journal Title

      Nature Cell Biology

      Volume: 23 Issue: 9 Pages: 1002-1012

    • DOI

      10.1038/s41556-021-00745-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Piwi-piRNA complexes induce stepwise changes in nuclear architecture at target loci2021

    • Author(s)
      Iwasaki Yuka W、Sriswasdi Sira、Kinugasa Yasuha、Adachi Jun、Horikoshi Yasunori、Shibuya Aoi、Iwasaki Wataru、Tashiro Satoshi、Tomonaga Takeshi、Siomi Haruhiko
    • Journal Title

      The EMBO Journal

      Volume: 40 Issue: 18

    • DOI

      10.15252/embj.2021108345

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation2021

    • Author(s)
      Ishino Kyoko、Hasuwa Hidetoshi、Yoshimura Jun、Iwasaki Yuka W、Nishihara Hidenori、Seki Naomi M、Hirano Takamasa、Tsuchiya Marie、Ishizaki Hinako、Masuda Harumi、Kuramoto Tae、Saito Kuniaki、Sakakibara Yasubumi、Toyoda Atsushi、Itoh Takehiko、Siomi Mikiko C、Morishita Shinichi、Siomi Haruhiko
    • Journal Title

      Nucleic Acids Research

      Volume: 49 Issue: 5 Pages: 2700-2720

    • DOI

      10.1093/nar/gkab059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potent mouse monoclonal antibodies that block SARS-CoV-2 infection2021

    • Author(s)
      Guo Youjia、Kawaguchi Atsushi、Takeshita Masaru、Sekiya Takeshi、Hirohama Mikako、Yamashita Akio、Siomi Haruhiko、Murano Kensaku
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100346-100346

    • DOI

      10.1016/j.jbc.2021.100346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells2020

    • Author(s)
      Onishi Ryo、Sato Kaoru、Murano Kensaku、Negishi Lumi、Siomi Haruhiko、Siomi Mikiko C.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 50

    • DOI

      10.1126/sciadv.aaz7420

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of Drosophila Piwi.2020

    • Author(s)
      Yamaguchi, S., Oe, A., Nishida, KM., Yamashita, K., Kajiya, A., Hirano, S., Matsumoto, N., Dohmae, N., Ishitani, R., Saito, K., Siomi, H., Nishimasu, H., Siomi, MC., and Nureki, O.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 858-858

    • DOI

      10.1038/s41467-020-14687-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing2019

    • Author(s)
      Murano, K., Iwasaki Y.W., Ishizu H., Mashiko, A., Shibuya, A., Kondo, S., Adachi, S., Suzuki, S., Saito, K., Natsume, T., Siomi, M.C., Siomi, H.
    • Journal Title

      The EMBO Journal

      Volume: 印刷中 Issue: 17 Pages: 1-20

    • DOI

      10.15252/embj.2019102870

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Broad Heterochromatic Domains Open in Gonocyte Development Prior to De Novo DNA Methylation2019

    • Author(s)
      Yamanaka Soichiro、Nishihara Hidenori、Toh Hidehiro、Eijy Nagai Luis Augusto、Hashimoto Kosuke、Park Sung-Joon、Shibuya Aoi、Suzuki Ana Maria、Tanaka Yujiro、Nakai Kenta、Carninci Piero、Sasaki Hiroyuki、Siomi Haruhiko
    • Journal Title

      Developmental Cell

      Volume: 51 Issue: 1 Pages: 21-34

    • DOI

      10.1016/j.devcel.2019.07.023

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential roles of Windei and nuclear monoubiquitination of Eggless/ SETDB 1 in transposon silencing2019

    • Author(s)
      Osumi Ken、Sato Kaoru、Murano Kensaku、Siomi Haruhiko、Siomi Mikiko C
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 12

    • DOI

      10.15252/embr.201948296

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Embryonic development requires transposon expression2023

    • Author(s)
      H Siomi
    • Organizer
      Keystone meeting, “Transposable elements at the crossroads of evolution, health and disease,”
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of endogenous retrovirus MERVL in early embryos2023

    • Author(s)
      H Siomi
    • Organizer
      UBC Advanced Genomics and Genome Engineering Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transposons play key role in ZGA2023

    • Author(s)
      H Siomi
    • Organizer
      2023 Taiwan-Japan Bilateral Meeting on RNA and Biofunctions,
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Preimplantation embryo development requires transposable element expression2023

    • Author(s)
      H. Siomi
    • Organizer
      Small Regulatory RNAs: from biogenesis to function @ Montpellier
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PIWIs in the hamster ovary2022

    • Author(s)
      H. Siomi
    • Organizer
      EMBO piRNA Workshop 2022 on PIWI proteins and piRNAs
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transposable elements in mouse early embryos2022

    • Author(s)
      H. Siomi
    • Organizer
      Cell Research Symposia on Molecular Science-Non-coding and Regulatory RNA
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Embryo development requires transposable element expression2022

    • Author(s)
      H. Siomi
    • Organizer
      The International Symposium “Totipotency and Germ Cell Development”
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] TDP-43 safeguards the embryonic genome from L1 transposition2022

    • Author(s)
      H. Siomi
    • Organizer
      The 67th Annual Meeting of the Japan Society of Human Genetics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウスを相補する実験動物としてのハムスターの利用2021

    • Author(s)
      塩見春彦
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 古くて新しい実験動物:ハムスター2021

    • Author(s)
      塩見春彦
    • Organizer
      日本RNAi研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新しいモデル動物としてのハムスター2021

    • Author(s)
      塩見春彦
    • Organizer
      日本薬学会第141年会 特別講演
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Golden hamster: New model animal to study the piRNA pathway in mammalian oocytes2020

    • Author(s)
      塩見春彦
    • Organizer
      Cold Spring Harbor Laboratory meeting on Regulatory & Non-coding RNAs,
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 日本におけるゲノム合成2020

    • Author(s)
      塩見春彦
    • Organizer
      The BBSRC-JST UK-Japan Virtual Workshop in Synthetic Biology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Golden hamster as a new model to study the piRNA pathway2019

    • Author(s)
      塩見春彦
    • Organizer
      Institute of Biochemistry and Cell Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetic modifications during mouse gonocyte development2019

    • Author(s)
      塩見春彦
    • Organizer
      School of Life Science and Technology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The piRNA pathway in mammals2019

    • Author(s)
      塩見春彦
    • Organizer
      NIG Meeting on chromosome
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Piwi-mediated epigenetic modifications in Drosophila2019

    • Author(s)
      塩見春彦
    • Organizer
      60th Niigata Biochemistry Meeting
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Mammalian Piw-piRNA pathways2019

    • Author(s)
      塩見春彦
    • Organizer
      The 5th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Mammalian Piw-piRNA pathways2019

    • Author(s)
      塩見春彦
    • Organizer
      NIBS/National Institutes of Biological Sciences
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA methylation during mouse gonocyte development2019

    • Author(s)
      塩見春彦
    • Organizer
      The 11th JARI annual meeting
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Transposable elements and genome evolution2019

    • Author(s)
      塩見春彦
    • Organizer
      Nippon IBM Amagi Center
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Piwi-mediated transposon silencing2019

    • Author(s)
      塩見春彦
    • Organizer
      RNA frontier meeting
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Small RNA-mediated gene silencing2019

    • Author(s)
      塩見春彦
    • Organizer
      Cheminas 40
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Transposon silencing in mammalian gonads2019

    • Author(s)
      塩見春彦
    • Organizer
      Institute of Molecular Embryology and Genetics
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Transposon exaptation2019

    • Author(s)
      塩見春彦
    • Organizer
      Institute of Advanced Medical Sciences
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Remarks] Siomi Lab

    • URL

      http://siomilab.med.keio.ac.jp/

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks] Keio University WPI-Bio2Q

    • URL

      https://bio2q.keio.ac.jp/

    • Related Report
      2023 Annual Research Report

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Published: 2019-07-04   Modified: 2025-01-30  

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