基本状態の多能性の転写的および表遺伝子学的基礎

Hendrik Marks¹, Tüzer Kalkan, Roberta Menafra

¹Department of Molecular Biology, Faculty of Science, Radboud University, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Cell

|May 1, 2012

まとめ

マウス胚性幹細胞 (ESC) の血清は,2i媒質の細胞よりも多くの多様性を示しています. 2i状態は,素朴な基底状態と考えられ,異なった転写および表遺伝的プロフィールを明らかにします.

科学分野:

発達生物学発達生物学について
幹細胞生物学幹細胞生物学
エピジェネティクスエピジェネティクス

背景:

血清で培養された胚性幹細胞 (ESC) は異質性を示す.
2i媒介 (MekとGSK3阻害剤) は,ESCにおけるナイブ基底状態を誘導することを提案しています.
異なる分子プロフィールは,ESC州の違いを裏付ける可能性があります.

研究の目的:

血清で培養されたマウスのESCのトランスクリプトミクスとエピジェノミクスプロフィールを,2i媒介と比較する.
2i.によって誘発された提案されたネイブグラウンドステートの特徴を調査する.
異なるESC培養条件における遺伝子発現を制御する規制メカニズムを理解する.

主な方法:

ESCのトランスクリプトームプロファイリング (RNAシーケンシング)
ヒストンの改変分析 (例えば,H3K27me3) とクロマチンのアクセシビリティを含むエピジェノームプロファイリング.
遺伝子発現パターンとクロマチンの状態の評価.
差別化可能性を評価するための機能的分析.

主要な成果:

血清および2i培養されたESCは,異なったトランスクリプトームおよび表遺伝子プロファイルを示します.
2iで処理されたESCは,遺伝子の発現が低下し,抑制性ヒストンマーク (H3K27me3) と二価ドメインが少なくなります.
エピジェネティックの違いにもかかわらず,両方の培養条件は,類似の差別化可能性を持つESCを生成します.
RNAポリメラーゼIIの一時停止は,2i条件化されたESCにおける早期発達の遺伝子転写を抑制する.

結論:

素朴な基底状態は,転写増強と許容性染色体によって特徴付けられます.
基底状態からの脱出は,メタステーブルな中間または多世代プリミングを必要としない場合があります.
ESC状態を理解することは,発達生物学と再生医療の研究にとって極めて重要です.

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