細胞内α-ケトグルタレートは,胚性幹細胞の多能性を維持する
Bryce W Carey1, Lydia W S Finley2, Justin R Cross3
1Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065, USA.
Nature
|December 10, 2014
まとめ
マウスの胚性幹細胞は,細胞内アルファケトグルタレート (αKG) とサクシネートレベルを調節することによって多能性を維持します. この代謝バランスは,幹細胞のアイデンティティと自己再生に不可欠な表遺伝的変化に影響を与えます.
科学分野:
- 細胞の代謝について
- エピジェネティクス エピジェネティクス
- 幹細胞生物学 幹細胞生物学
背景:
- 細胞増殖と分化における細胞代謝の役割は完全に理解されていません.
- ほとんどの哺乳類の細胞は,不必要であるにもかかわらず,増殖のためにグルタミンを必要とします.
研究 の 目的:
- マウスの胚性幹細胞 (ES) が多能性を維持するための代謝要件を調査する.
- 幹細胞のアイデンティティを調節する細胞内アルファケトグルタレート (αKG) とサクシネートの役割を調査する.
主な方法:
- ネズミのES細胞をナイブ多能性を維持する条件下で培養する.
- グルコースとグルタミン類の分解を含む細胞代謝の測定.
- 細胞内αKGとサクシネート濃度と,その影響が表遺伝子変異に及ぼす影響を分析する.
主要な成果:
- ネイブマウスのES細胞は,外因的なグルタミン酸がなければ増殖しますが,利用可能なときにそれを消費します.
- ES細胞は高細胞内αKGレベルを維持し,αKG/サッキナート比率が上昇する.
- この比率はヒストロン/DNA脱メチル化を促進し,多能性と自己再生をサポートします.
結論:
- 細胞内αKG/サクシネートレベルは,幹細胞の同一性と多能性を維持するために重要である.
- エピジェネティック変異の代謝調節は,幹細胞の転写およびエピジェネティック状態においてメカニズム的な役割を果たします.
- αKGはES細胞の自己再生をサポートし,サッキナートは分化を促進します.
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