人間の誘発性多能幹細胞における異常な表遺伝子学的再プログラミングのホットスポットである
Ryan Lister1, Mattia Pelizzola, Yasuyuki S Kida
1Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|February 4, 2011
まとめ
誘発性多能幹細胞 (iPSCs) は,体細胞記憶を保持し,DNAメチル化再プログラムにおいて有意な変動性を示しています. これらの再プログラミングシグネチャは,微分化後も持続し,再生医療での使用に影響を与えます.
科学分野:
- 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
- ゲノミクスゲノミクスとは
背景:
- 誘導性多能幹細胞 (iPSC) は,体細胞を再プログラムすることによって生成され,再生医療のための胚性幹細胞 (ES) を模倣することを目的としています.
- エピジェノミック再構成は,このプロセスの鍵ですが,DNAメチル化パターンの回復の完全性は不明です.
研究 の 目的:
- ES細胞と体細胞と比較して,ヒトのiPSCの全ゲノムDNAメチル化パターンを包括的に分析する.
- ES細胞のようなDNAメチル化の回復の範囲を調査し,潜在的な再プログラムエラーを特定する.
主な方法:
- 単塩基解像度での全ゲノムDNAメチル化プロファイリングは,5つのヒトiPSCラインで行われました.
- 比較のために,マッチしたES細胞,体細胞,および分化されたiPSC/ES細胞のメチロームを分析した.
主要な成果:
- 人間のiPSCは,保持された"体内記憶"と異常なDNAメチル化を含む,重要な再プログラミングの変動性を表しています.
- セントロメアとテロメア付近の共有メガベーススケールの微分メチル化領域は,非CGメチル化の不完全な再プログラムを示しています.
- iPSCsとES細胞の間でCGメチル化とヒストン変異の違いが観察されました.
結論:
- iPSCの変性の再プログラミングは,ES細胞のようなDNAメチル化パターンの不完全な回復につながります.
- CGメチル化再プログラミングのエラーは,差異化中に頻繁に伝達され,持続的なiPSC再プログラミングシグネチャを確立します.
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