幹細胞 幹細胞とは m6A mRNAメチル化は,微分化に向けての素朴な多能性の解消を促進します
Shay Geula1, Sharon Moshitch-Moshkovitz2, Dan Dominissini3
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
まとめ
mRNAを修飾する酵素であるMettl3は,マウスの先天性多能性の終結に不可欠である. その欠如は,失敗した状態の終結と異常な系統のプリミングにより,胚の致死性を引き起こします.
科学分野:
- エピジェネティクス エピジェネティクス
- 発達生物学 発達生物学とは
- 幹細胞生物学 幹細胞生物学
背景:
- 胚性幹細胞の多能性は,異なるネイブ状態とプライム状態で存在します.
- ネイヴ・プルリポテンシーとプライム・プルリポテンシーの間の移行の調節は,まだ完全に理解されていません.
研究 の 目的:
- 原始的な多能性の終結を制御する分子調節体を特定する.
- プラリポテンシー状態の移行におけるN(6) -メチラデノシン (m(6) A) 変異の役割を調査する.
主な方法:
- Mettl3 ノックアウトマウインモデル (プリインプランテーションエピブラストと胚性幹細胞) の生成.
- m(6) mRNA.Aのレベルを分析する.
- プラリポテンシー状態の終結と系統のプリミングの評価.
- 移植後の段階における胚死亡率の評価.
主要な成果:
- Mettl3のノックアウト細胞は,mRNA m(6) Aのレベルが低下しているが,生存可能である.
- これらの細胞は,素朴な多能性の状態を終わらせることが出来ません.
- 異常で制限された系統のプライミングが発生し,早期の胚性致死につながる.
- m(6) 修正は主に,先天的な多能性を促進するものを含むmRNAの安定性を低下させる.
結論:
- Mettl3は,マウリンの先天性多能性の早期終止に不可欠です.
- m(6) AによるmRNAの表遺伝的変異は,多能性を調節する上で重要なインビオの役割を果たします.
- 識別された規制モジュールは,ナイブ状態とプライムされた多能性状態を機能的に反対します.
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