Establishment of basic technologies for developmental engneering using transplantation of spermatogenic stem cells in chicken

• Project/Area Number: 18K14570
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Hiroshima University
• Principal Investigator: Nakamura Yoshiaki 広島大学, 統合生命科学研究科(生), 助教 (30613723)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ニワトリ / マウス / 始原生殖細胞 / 精子幹細胞 / 移植 / 発生工学

Outline of Final Research Achievements

This study was conducted to improve research infrastructure in the field of chicken developmental engineering using transplantation of spermatogonial stem cells (SSCs). Using chicken as a model, an effective method for removal of endogenous germ cells was developed. The feasibility of this method for chicken SSC transplantation are to be evaluated in near future but is available for transplantation of primordial germ cells, progenitor cells for SSCs. To establish a strategy to improve SSC transplantation, fate behavior of individual SSCs were analyzed in mouse. As a result, transplanted SSCs follow stochastic fate and a major fraction of them were lost through differentiation and cell death. Based on this finding, SSC transplantation efficiency was dramatically improved by inhibiting differentiation of transplanted SSCs. To apply this strategy to chicken SSC transplantation, an approach to inhibit differentiation of chicken SSCs to be explored in near feature.

Academic Significance and Societal Importance of the Research Achievements

マウスで開発された精子幹細胞の移植法は、遺伝的多様性の保全や男性不妊治療への応用が期待されている。ニワトリにおいても精子幹細胞移植の成功例はあるが、実用レベルには達していない。本研究で開発したニワトリ生殖細胞の効率的な除去法は、精子幹細胞の移植に利用可能か検討中であるものの、始原生殖細胞の移植には利用可能であった。また、マウスで確立した精子幹細胞の移植効率を改善する方法論は、定説を覆すものであり、特にがん治療後の妊孕性回復へ貢献することが期待される。本研究では、この方法論がニワトリ精子幹細胞移植へ応用できるか結論を出すに至らなかったため、今後多角的なアプローチで検討を進める必要がある。

Research Products

• [Int'l Joint Research] University of Cambridge(英国)
• [Journal Article] Transient suppression of transplanted spermatogonial stem cell differentiation restores fertility in mice (2021)
  • Author(s): Nakamura Y, Jorg DJ, Kon Y, Simons BD, Yoshida S
  • Journal Title: Cell Stem Cell Volume: 28 Issue: 8 Pages: 1-14
  • DOI: 10.1016/j.stem.2021.03.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ニワトリ始原生殖細胞に適した凍結保存液の開発 (2021)
  • Author(s): 濵井奈津子, 小出茅洋, 都築政起, 中村隼明
  • Organizer: 日本畜産学会第128回大会
• [Presentation] 宿主精巣に移植した精子幹細胞はストカスティックな運命を辿る (2020)
  • Author(s): 中村隼明, David J Jorg, Benjamin D Simons, 吉田松生
  • Organizer: 第113回日本繁殖生物学会大会
• [Presentation] Impact of KnockOut Serum Replacement in the culture of chicken primordial germ cells (2019)
  • Author(s): Chihiro Koide, Natsuko Hamai, Effrosyni Fatira, Sigeru Nomura, Atsushi Takenouchi, Masaoki Tsudzuki, Yoshiaki Nakamura
  • Organizer: 日本畜産学会第126回大会
• [Presentation] ニワトリ始原生殖細胞の緩慢凍結に用いる凍結保護剤の比較選定 (2019)
  • Author(s): 濵井奈津子, 小出茅洋, 野村茂, 竹之内惇, 都築政起, 中村 隼明
  • Organizer: 日本畜産学会第126回大会
• [Presentation] 家禽類および齧歯類における生殖細胞の移植を用いたキメラ作製技法 (2018)
  • Author(s): 中村隼明
  • Organizer: 第111回日本繁殖生物学会大会
  • Invited