Dynamic maintenance mechanisms of differentiation states in pluripotent stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Toho University (2022); Osaka University (2019-2021)
• Principal Investigator: Yamaguchi Shinpei 東邦大学, 理学部, 講師 (80740795)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 2細胞期胚様細胞 / ES細胞 / 初期胚 / Zscan4 / p53 / Pum3 / Tet1 / クロモセンター

Outline of Final Research Achievements

Embryonic stem cells (ES cells), undifferentiated cells with the capacity to differentiate into all cell types, harbor a small population of highly undifferentiated cells known as 2-cell-like cells, which express the transcription factor Zscan4. However, the mechanisms underlying their transition were largely unknown. In this study, we discovered that the nucleolar protein Pum3 is involved in this transition. Pum3 deficiency induced ribosome stress and activated p53. These findings highlight the importance of p53 activation in the transition to 2-cell-like cells. Furthermore, we identified that the chromocenter, a nuclear structure, is lost in 2-cell-like cells. We also uncovered the involvement of DNA demethylation factor Tet1 and polycomb in the regulation of chromocenter structure.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

この研究はES細胞の2細胞期胚様細胞の移行メカニズムやクロモセンターの制御に関する新たな知見を提供した。これの発見は再生医療や幹細胞の臨床応用に寄与するだけでなく、がんや遺伝子疾患の研究においても重要な情報となりうる。特に、ES細胞の未分化状態やゲノムの安定性に関わる分子メカニズムの解明は、がんの発生や進行における異常な細胞分化やゲノム不安定性の理解に寄与する。また、クロモセンターの制御に関する知見は、遺伝子の正確な制御やゲノムの安定性に関連し、遺伝子疾患のメカニズムや治療法の開発に向けた手がかりとなる。これらの成果は学術誌に公開済みであり、生命科学の深化に寄与すると期待している。