Metabolic and epigenetic regulation of pluripotency via FLCN-RAG-TFE axis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06693
• 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: Kumamoto University
• Principal Investigator: Endoh Mitsuhiro 熊本大学, 発生医学研究所, 助教 (40391883)
• Co-Investigator(Kenkyū-buntansha): 須田 年生 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 多能性幹細胞 / 胚性幹細胞 / ES細胞 / 多能性 / リソソーム / 転写因子 / 多能性 / 初期発生

Outline of Final Research Achievements

Deletion of Flcn in ES cells resulted in permanent nuclear localization of Tfe3 and LIF-independent self-renewal, whereas further deletion of Tfe3 resulted in loss of this phenotype. Forced activation of Tfe3 also resulted in the LIF-independent self-renewal phenotype, and this phenotype was dependent on the naive pluripotency factors Esrrb and Nanog. Since ES cells deficient in both Tfe3 and Tfeb could not be established and maintained, Tfe3/Tfeb may contribute to ES cell maintenance in a coordinated manner. Mouse blastocysts with constitutively activated TFE3 could be maintained for a certain period of time in vitro, suggesting that TFE3 may contribute to the maintenance of preimplantation embryos.

Free Research Field

幹細胞

Academic Significance and Societal Importance of the Research Achievements

マウスES細胞および初期胚を用いた研究を通して、リソソーム生合成のマスター転写因子であるTFE3を活性化させることにより、着床前胚の多能性状態を維持することが可能であることが分かった。この研究成果は、リソソームを介したエネルギー代謝活性の変化が多能性の遷移に関与する可能性を明らかにした点において、学術的に重要な知見である。