Post-transcriptional control of spermatogonial stem cell self-renewal and differentiation

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Yokohama City University
• Principal Investigator: KUROHA Kazushige 横浜市立大学, 医学部, 助教 (50580015)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 精子幹細胞 / 翻訳制御 / エピジェネティクス

Outline of Final Research Achievements

During the period when spermatogonial stem cells lose their self-renewal activity, significant epigenetic changes occur in them. It is suggested that epigenetic modification enzymes, such as DNA methyltransferase and histone methyltransferase, are upregulated through post-transcriptional regulation. In this study, our aim was to investigate the translational regulation of epigenetic modification enzymes during the transition from spermatogonial stem cells to progenitors. We found that 1) mRNA export from the nucleus and its localization within cells, 2) the upregulation of total protein synthesis and the specific activation of mTOR during differentiation, were not sufficient for the induction of epigenetic modification enzymes. Thus, the upregulation of these enzymes is likely to be achieved through selective regulatory mechanisms rather than being accompanied by fluctuations in overall protein synthesis.

Free Research Field

精子幹細胞と翻訳

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。