Evolutional origin and transformation of transcriptional networks for the conversion from pluripotent cells into primordial germ cells

• Project/Area Number: 18H02422
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Kwansei Gakuin University
• Principal Investigator: SEKI YOSHIYUKI 関西学院大学, 生命環境学部, 教授 (20435655)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 多能性幹細胞 / 生殖細胞 / エピジェネティクス / 始原生殖細胞 / 転写因子ネットワーク / 多能生 / 多能性細胞 / イベリアトゲイモリ / エンハンサー / ES細胞 / iPS細胞 / エピゲノム / ゲノム

Outline of Final Research Achievements

The pluripotent cells are established in the early embryo during the development of multicellular organisms. In this study, we tried to compare the transcriptional networks for converting from pluripotent cells into primordial germ cells. We provided evidence that Prdm14, an essential factor for germ cell specification in mice, is critical for the early development of newt embryos. Furthermore, we identified that the transient downregulation of PRDM14 expression is vital for human germ cell specification.

Academic Significance and Societal Importance of the Research Achievements

多能性細胞の成立・維持及び始原生殖細胞形成を制御する転写因子ネットワークにはマウスとヒトで保存されていない構成成分が多く存在する。本研究において、転写因子PRDM14がイモリにおいて初期発生に重要であることが明らかとなったため、四肢動物全般においてPRDM14は初期発生に重要である可能性及びマウス特異的に重要性が消失した可能性が考えられる。また、多能性幹細胞は哺乳類のみで樹立が成功しているが、本研究の成果は、有尾両生類の多能性幹細胞の樹立に繋がる可能性が期待できる。

Research Products

• [Int'l Joint Research] ノッティンガム大学(英国)
• [Journal Article] The PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during the transition from primed to naiive pluripotency (2020)
  • Author(s): Maiko Yamamoto, Yoshiaki Suwa, Kohta Sugiyama, Naoki Okashita, Masanori Kawaguchi, Naoki Tani, Kazumi Matsubara, Akira Nakamura and Yoshiyuki Seki
  • Journal Title: Journal of Cell Science Volume: 133 Issue: 15 Pages: 1-13
  • DOI: 10.1242/jcs.240176
  • Peer Reviewed / Open Access
• [Journal Article] Co-option of the PRDM14-CBFA2T complex from motor neurons to pluripotent cells during vertebrate evolution (2019)
  • Author(s): Masanori Kawaguchi, Kota Sugiyama, Kazumi Matsubara, Che-Yi Lin, Shigehiro Kuraku, Shota Hashimoto, Yoshiaki Suwa, Luok Wen Yong, Koji Takino, Shota Higashida, Daisuke Kawamura, Jr-Kai Yu and Yoshiyuki Seki
  • Journal Title: Development Volume: 146 Pages: 1-14
  • DOI: 10.1242/dev.168633
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Maintenance of cell fates and regulation of the histone variant H3.3 by TLK kinase in Caenorhabditis elegans (2019)
  • Author(s): Yukimasa Shibata, Yoshiyuki Seki, Kiyoji Nishiwaki
  • Journal Title: Biology Open Volume: 8(1) Pages: 1-12
  • DOI: 10.1242/bio.038448
  • Peer Reviewed
• [Presentation] 基底状態ES細胞におけるDNA脱メチル化機構の解明 (2021)
  • Author(s): 丸谷美結
  • Organizer: 日本遺伝学会第93回大会
• [Presentation] 多能性ネットワークの進化的起源と変容 (2019)
  • Author(s): 関 由行
  • Organizer: 第91回日本遺伝学会年会
  • Invited
• [Presentation] 胚性ゲノム活性化を保証するエピゲノム制御の階層性 (2019)
  • Author(s): 関 由行
  • Organizer: 第42回日本分子生物学会年会
  • Invited
• [Presentation] 多能性ネットワークの進化的起源と変容 (2018)
  • Author(s): 関 由行
  • Organizer: 日本遺伝学会第90回大会
• [Presentation] CtBP1/2 is a gatekeeper for ground state pluripotency and totipotency (2018)
  • Author(s): Yoshiyuki Seki
  • Organizer: EMBO workshop From epigenome towards epitranscriptome in cell fate choice
  • Int'l Joint Research
• [Remarks] 多能性幹細胞のプライム型からナイーブ型への変換機構の解明
  • URL: https://www.kwansei.ac.jp/news/detail/4158
• [Remarks] 関研究室ホームページ
  • URL: https://seki-lab.wixsite.com/seki-lab