Chd1は,オープンクロマチンと胚性幹細胞の多能性を調節する

Alexandre Gaspar-Maia¹, Adi Alajem, Fanny Polesso

¹Department of Ob/Gyn and Pathology, Center for Reproductive Sciences and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0525, USA.

Nature

|July 10, 2009

まとめ

クロマチンのリモデレータChd1は,胚性幹細胞におけるクロマチンの開放を維持しており,これは多能性と分化に極めて重要です. 欠乏すると,幹細胞の潜在能力と体細胞の再プログラムが損なわれます.

科学分野:

幹細胞生物学幹細胞生物学とは
エピジェネティクスエピジェネティクス
クロマチンの改造

背景:

オープンクロマチンは,多能幹細胞の特徴である.
クロマチンと多能性を保持する分子メカニズムは完全に理解されていません.

研究の目的:

マウスの胚性幹細胞におけるクロマチンの開放性および多能性の維持におけるクロマチンの改造因子Chd1の役割を調査する.
Chd1が幹細胞の分化能力と体細胞の再プログラムに不可欠であるかどうかを判断する.

主な方法:

胚性幹細胞におけるChd1の局所化を研究した.
Chd1のダウンレギュレーションがクロマチンの構造と遺伝子発現に与える影響を評価した.
Chd1欠乏性幹細胞の分化能力を評価した.
Chd1.1がない場合の体細胞再プログラミングの効率を検証した.

主要な成果:

Chd1は,活性遺伝子プロモーターに関連したユークロマチンタンパク質です.
Chd1のダウンレギュレーションは,ヘテロクロマチンの蓄積と多能性の喪失につながる.
Chd1欠乏した幹細胞は,原始的な内皮に分化する能力を失い,神経分化が増加しています.
Chd1は,繊維芽細胞を多能状態に効率的に再プログラムするために不可欠です.

結論:

Chd1は,胚性幹細胞におけるクロマチンの開閉性と多能性を維持するために不可欠である.
Chd1は,幹細胞の分化と体細胞の再プログラムの両方で重要な役割を果たしています.

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