Translational regulation of epigenetic factors in spermatogonial stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23831
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Yokohama City University
• Principal Investigator: KUROHA Kazushige 横浜市立大学, 医学部, 助教 (50580015)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 精子幹細胞 / エピジェネティクス / 翻訳制御

Outline of Final Research Achievements

During the time when spermatogonial stem cells loss their stem cell activity, significant epigenetic changes occur in them. It has been suggested that the enzymes involved in the global epigenetic change (hereinafter called “epigenetic factors”) may be upregulated by translational regulation. In this study, we aimed to investigate the translational regulation of epigenetic factors during the stem cell to progenitor transition. We found that 1) translation of the mRNAs encoding epigenetic factors is strongly repressed in spermatogonial stem cells, 2) different mRNA isoforms are expressed during the transition, and 3) mRNAs encoding epigenetic factors are localized in the cytoplasm regardless of the stem cell and differentiating cells, thus mRNA export from nucleus may not be crucial for the upregulation of epigenetic factors.

Free Research Field

精子幹細胞、翻訳制御

Academic Significance and Societal Importance of the Research Achievements

ゲノム修飾酵素の翻訳制御は、精子幹細胞から分化細胞の移行に必要なエピジェネティクス制御の上流にあると考えられ、そのメカニズムを理解することで、成体幹細胞に対して広く適用可能な『細胞運命の決定機構』を翻訳制御の視点で明らかにできると考えられる。これを達成することは、再生医療研究に重要なだけでなく、「多細胞生物における様々な種類の細胞がどのように生み出されるのか」といった生物学における根本の問いの解明につながると期待される。