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Establishment of induced Pluriotent Stem cells with genomic stability by zygotic transcriptional factors

Research Project

Project/Area Number 17H05100
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

YAMADA Mitsutoshi  慶應義塾大学, 医学部(信濃町), 講師 (40383864)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2019: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2018: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords胚性ゲノムの活性化 ZGA / iPS細胞 / 初期化 reprogramming / ゲノム安定性 / ES細胞 / 受精卵 / 生殖医学 / がん化 / 加齢 / ミトコンドリア / Zscan5b / ZGA / iPS / Reprogramming / 初期胚発生 / 卵子の加齢 / 初期化 / 胚性ゲノムの活性化
Outline of Final Research Achievements

Induced pluripotent stem cells (iPSCs)are expected to be useful for regenerative medicine such as drug screening and transplantation, which might particularly benefit older patients suffering from heart failure, diabetes and degenerative diseases. However, it is known that iPSCs isolated from aged somatic cells exhibit impaired genomic stability. In this study, we show that the Zygotic Genome Activation (ZGA) gene Zscan5b expressed from early embryonic development through the establishment process of embryonic stem cells (ESCs) and is involved in the genomic stability of ESCs. These results provide a new concept that loss of function of genes expressed in the early embryogenesis can lead to the loss of genomic stability of somatic and ES cells, resulting in random chromosomal aberrations. The findings would contribute to improve genomic stability of embryos and pluripotent stem cells, leading to the development of assisted reproduction technology and regenerative medicine.

Academic Significance and Societal Importance of the Research Achievements

本研究は、「受精後の初期に生じる遺伝子の機能を喪失させることで体細胞とESCsのゲノム安定性が損なわれ、ランダムに染色体異常が起こりえる」というあらたな概念を提示した。マウスモデルとヒトにおける遺伝子発現の時期は異なるため、本研究成果がそのままヒトに当てはまるかは今後さらなる検証が必要である。しかしながら今回の成果は、健全な受精卵の発育や幹細胞の樹立を通して、より安全な生殖補助医療および再生医療の実現に大きく寄与することが期待される。

Report

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

    (14 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.2019

    • Author(s)
      Ogawa S, Yamada M, Nakamura A, Sugawara T, Nakamura A, Miyajima S, Harada Y, Ooka R, Okawa R, Miyauchi J, Tsumura H, Yoshimura Y, Miyado K, Akutsu H, Tanaka M, Umezawa A, Hamatani T.
    • Journal Title

      Stem Cell Reports

      Volume: 12 Issue: 6 Pages: 1366-1379

    • DOI

      10.1016/j.stemcr.2019.05.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Zspi deficiency impairs DNA damage response and causes chromosomal aberrations during mitosis.2019

    • Author(s)
      Yamada M, Ogawa S, Nakamura A, Sugawara T, Miyado K, Akutsu H, Hamatani T, Umezawa A, Tanaka M
    • Organizer
      The 90th Royal College of Obstetriciaans & Gynaecologists (RCOG) World Congress.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MOUSE ZSCAN5B DEFICIENCY IMPAIRS DNA DAMAGE RESPONSE AND CAUSES CHROMOSOME ABERRATIONS DURING MITOSIS.2019

    • Author(s)
      Yamada M, Ooka R, Nakamura A, Sugawara T, Ogawa S, Miyado K, Akutsu H, Hamatani T, Tanaka M, Umezawa A.
    • Organizer
      The International Society for Stem Cell Research 17th Annual Meeting.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of new Assisted Reproductive Technology (ART) and regenerative medicine based on regulating gene expression during preimplantation development.2019

    • Author(s)
      Yamada Mitsutoshi
    • Organizer
      The 105th Annual Congress of Korean Society of Obstetrics & Gynaecologists (KSOG).
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Zspi-deficient vertebrate cells accumulate chromosomal gap and accelerates carcinogenesis in mice.2018

    • Author(s)
      Yamada M, Ogawa S, Hamatani T, Akutsu H, Umezawa A, Tanaka M.
    • Organizer
      The NYSCF conference. New York, USA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 卵子・初期胚発生のバイオロジーからみた不妊症2018

    • Author(s)
      山田 満稔
    • Organizer
      第20回大阪不妊の集い勉強会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 【シンポジウム】卵子間核置換は排卵後加齢卵子のfragmentationを防ぐことで発生能を改善させる2018

    • Author(s)
      山田 満稔
    • Organizer
      第36回日本受精着床学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 遺伝子発現からみた初期胚発生のバイオロジー2018

    • Author(s)
      山田 満稔
    • Organizer
      第17回生殖バイオロジー東京シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 新規SCAN-zinc finger遺伝子Zfp371は胚性ゲノム活性化に伴い発現し, 体細胞分裂過程におけるゲノムの安定性に関わる2017

    • Author(s)
      小川誠司、山田満稔、阿久津英憲、梅澤明弘、浜谷敏生、田中守
    • Organizer
      第35回日本受精着床学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 【シンポジウム】Rising Sun Lectureヒトtherapeutic cloningへの挑戦と課題2017

    • Author(s)
      山田満稔、阿久津英憲、Dieter Egli
    • Organizer
      第20回日本IVF学会・学術集会・
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 【シンポジウム】難治性疾患克服バイオロジー:生殖・発生・小児疾患を中心に ヒト生殖細胞系列におけるミトコンドリアゲノムの遺伝とミトコンドリア病遺伝予防を目指した卵子核移植の課題2017

    • Author(s)
      山田満稔、田中守、Dieter Egli
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Zspi-deficient vertebrate cells accumulate chromosomal gap and accelerates carcinogenesis in mice2017

    • Author(s)
      Seiji Ogawa, Yamada M, Hamatani T, Akutsu H, Tanaka M, Umezawa A
    • Organizer
      The International Society for Stem Cell Research 14th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Book] 先端医療シリーズ482017

    • Author(s)
      山田満稔、田中守
    • Total Pages
      529
    • Publisher
      先端医療技術研究所
    • Related Report
      2017 Annual Research Report
  • [Remarks] 受精卵・幹細胞のゲノム安定性の維持機構を解明-遺伝子による染色体構造の保護作用とDNA修復-

    • URL

      https://www.keio.ac.jp/ja/press-releases/2019/5/31/28-53422/

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2024-12-25  

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