Chromatin dynamics during primordial germ cell development in mammals

• Project/Area Number: 18H02613
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Yokobayashi Shihori 京都大学, iPS細胞研究所, 特定拠点講師 (20615736)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 始原生殖細胞 / 哺乳類 / エピゲノム / クロマチン高次構造 / 多能性幹細胞 / in vitro誘導系

Outline of Final Research Achievements

Primordial germ cells are the origin of mammalian germ cell lineage and undergo epigenomic reprogramming, including genome-wide DNA de-methylation. In this study, using mouse in vitro reconstitution systems, we comprehensively analyzed the epigenome, chromatin higher-order structure, and nuclear dynamics states on mouse pluripotent stem cells, epiblast-like cells, primordial germ cell-like cells, and spermatogonial stem cells. Our study revealed that primordial germ cells acquire characteristic higher-order chromatin states, and the chromatin changes are continuously maintained in spermatogonial stem cells.

Academic Significance and Societal Importance of the Research Achievements

生殖細胞は次世代に受け継がれる唯一の細胞系譜である。この継承を可能とするためにどのようなプログラムが生殖細胞発生過程に組み込まれているのか理解することは、発生研究分野の重要課題である。しかし、その希少性から、生体内試料を用いた解析手法には限界がある。本研究では、生殖細胞発生過程でおきる核クロマチン変化を理解するため、マウス試験管内再構成系を種々のクロマチン関連解析に適用することにより、生体内試料では非常に困難な包括的解析を高精度に行った。本研究で得られた知見および取得したデータは、今後の生殖細胞研究の発展に大いに貢献すると考えられる。

Research Products

• [Int'l Joint Research] McGill University(カナダ)
• [Int'l Joint Research] University of Pennsylvania/University of Colorado Boulder/Washington University School of Medicine(米国)
• [Int'l Joint Research] IMBA(オーストリア)
• [Journal Article] Nucleome programming is required for the foundation of totipotency in mammalian germline development (2022)
  • Author(s): Nagano Masahiro, Hu Bo, Yokobayashi Shihori et al.
  • Journal Title: The EMBO Journal Volume: 41 Issue: 13
  • DOI: 10.15252/embj.2022110600
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells (2021)
  • Author(s): Yokobayashi Shihori、Yabuta Yukihiro、Nakagawa Masato、Okita Keisuke、Hu Bo、Murase Yusuke、Nakamura Tomonori、Bourque Guillaume、Majewski Jacek、Yamamoto Takuya、Saitou Mitinori
  • Journal Title: Cell Reports Volume: 37 Issue: 5 Pages: 109909-109909
  • DOI: 10.1016/j.celrep.2021.109909
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of human oogonia from induced pluripotent stem cells in culture (2020)
  • Author(s): Yamashiro Chika、Sasaki Kotaro、Yokobayashi Shihori、Kojima Yoji、Saitou Mitinori
  • Journal Title: Nature Protocols Volume: 15 Issue: 4 Pages: 1560-1583
  • DOI: 10.1038/s41596-020-0297-5
  • Peer Reviewed
• [Journal Article] Reconstitution of Germ Cell Development In Vitro (2018)
  • Author(s): Shihori Yokobayashi and Mitinori Saitou
  • Journal Title: Cell Biology of the Ovary Volume: 1 Pages: 1-19
  • DOI: 10.1007/978-981-10-7941-2_1
  • ISBN: 9789811079405, 9789811079412
• [Journal Article] Generation of human oogonia from induced pluripotent stem cells in vitro. (2018)
  • Author(s): 30.Yamashiro C, Sasaki K, Yabuta Y, Kojima Y, Nakamura T, Okamoto I, Yokobayashi S, Murase Y, Ishikura Y, Shirane K, Sasaki H, Yamamoto T, Saitou M.
  • Journal Title: Science Volume: 362(6412) Issue: 6412 Pages: 356-360
  • DOI: 10.1126/science.aat1674
  • Peer Reviewed
• [Presentation] ヒトiPS細胞株におけるエピゲノム多様性の基底をなすゲノム特性の同定 (2022)
  • Author(s): 横林しほり
  • Organizer: 第74回日本細胞生物学会大会
  • Invited
• [Presentation] ヒト生殖細胞分化系構築を目指した多能性幹細胞の多様性解析 (2022)
  • Author(s): 横林しほり
  • Organizer: 2022年度国立遺伝学研究所クロマチン研究会
  • Invited
• [Presentation] Nucleome programming is required for the foundation of totipotency in mammalian germline development (2022)
  • Author(s): 長野眞大
  • Organizer: 第45回日本分子生物学会年会
• [Presentation] Nucleome programming for mammalian germ cell development. (2022)
  • Author(s): Masahiro Nagano
  • Organizer: EMBO Japan Virtual Lectures, Molecular basis of epigenetic inheritance and totipotency
  • Int'l Joint Research / Invited
• [Presentation] Nucleome Programming for the Foundation of Totipotency in Mouse Germline Development (2022)
  • Author(s): 長野眞大
  • Organizer: 2022年遺伝研研究会、有性生殖における染色体・クロマチン・核動態に関する若手研究者の会
  • Invited
• [Presentation] Nucleome Programming for Mouse Germ Cell Development In Vitro. (2021)
  • Author(s): Nagano M., Hu B., Yokobayashi S., Umemura F., Yamamura A., Ishikura Y., Yabuta Y., Ohta H., Saitou M.
  • Organizer: ASHBi Retreat 2021
• [Presentation] Inherent Genomic Properties Underlie the Epigenetic Heterogeneity of Human Induced Pluripotent Stem Cells. (2021)
  • Author(s): Shihori Yokobayashi
  • Organizer: ASHBi Retreat 2021
• [Presentation] Epigenetic variations of human induced pluripotent stem cells and their implications in their propensity for germ cell development. (2020)
  • Author(s): Shihori Yokobayashi
  • Organizer: 第43回日本分子生物学会
  • Invited
• [Presentation] マウス始原生殖細胞発生過程におけるエピゲノム再編成に伴うクロマチン構造変化の解明 (2019)
  • Author(s): Masahiro Nagano, Bo Hu, Shihori Yokobayashi, Akitoshi Yamamura, Yukiko Ishikura, Yukihiro Yabuta, Hiroshi Ohta, Mitinori Saitou
  • Organizer: 六甲医学研究会