プラリポテンス中のTRF2独立の染色体末端保護

Phil Ruis¹, David Van Ly^2,3, Valerie Borel¹

¹The Francis Crick Institute, London, UK.

Nature

|November 26, 2020

まとめ

テロメア保護は多能幹細胞と体組織によって異なります. TRF2タンパク質は,体細胞とは異なり,それなしでTループを形成する胚性幹細胞に欠かせない.

科学分野:

細胞生物学
遺伝学
発達生物学

背景:

哺乳類のテロメアはシェルテリン複合体を通して染色体の末端を保護する.
TRF2 (TERF2) は,体細胞のテロメア保護,Tループの形成,エンドツーエンドの融合の防止に不可欠です.
体細胞におけるTRF2の喪失は,テロメアの脱保護,染色体融合,細胞死につながる.

研究の目的:

多能胚性幹細胞 (ES) のテロメア保護におけるTRF2の役割を調査する.
多能細胞と体細胞のテロメア保護機構を比較する.
ES細胞では TRF2 が不要である理由を理解する.

主な方法:

マウスの胚性幹細胞におけるTRF2の削除
テロメアの整合性,DNA損傷反応,Tループ形成の分析
Trf2-null 胚とプラリポテンシーを終了する細胞の評価

主要な成果:

TRF2は,マウスES細胞のテロメア保護には欠かせません.
ES細胞はTRF2から独立してTループを形成する.
Trf2-null胚は,非多能細胞でのアポトーシスで植え付け前に停止する.
プラリポテンシーを終了した細胞は,TRF2依存のテロメア保護を迅速に採用する.

結論:

テロメアの保護メカニズムは,多能性および体性哺乳類の組織間で有意に異なります.
TRF2は分化細胞におけるテロメア末端の保護に不可欠であるが,多能幹細胞ではそうではない.
ES細胞がTRF2から独立してTループを形成する能力は,多能性期間の無用性を説明する.

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