青春期のエピジェネティック情報を回復し,視力を回復させるための再プログラム

Yuancheng Lu¹, Benedikt Brommer^2,3, Xiao Tian¹

¹Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA.

Nature

|December 3, 2020

まとめ

科学者は特定の遺伝子再プログラムを使ってマウスの目の青春期の表遺伝子パターンを復元しましたこれは視力や神経再生の改善で組織は老化の影響を逆転させる情報を保持していることを示唆しています

科学分野:

エピジェネティクスと老化に関する研究
神経科学と再生医療
分子生物学と遺伝子発現

背景:

加齢は組織機能障害と再生能力の喪失につながり部分的に表遺伝的騒音の蓄積が原因です
DNAのメチル化パターンは年齢とともに変化し老化時計の基礎となります
老化した組織が若々しい表遺伝子パターンを回復し,機能を改善するための情報を保持するかどうかは不明です.

研究の目的:

老いたマウスの網膜細胞に特定の遺伝子を再プログラムすることで青春期の表遺伝子パターンと機能を回復できるか調べる
この再プログラムによって組織再生が促進され老化による視力喪失が逆転するかどうかを調べる
OSK誘発による再プログラム効果におけるDNAデメチラゼTET1とTET2の役割を調査する.

主な方法:

Oct4 (Pou5f1),Sox2およびKlf4遺伝子 (OSK) の子宮外発現はマウスの網膜のギャングリオン細胞にみられる.
DNAメチル化パターンとトランスクリプトームの分析により,表遺伝子修復を評価する.
損傷後の軸索再生と視力の回復の評価緑内障と老いたマウスモデル
TET1とTET2のDNAデメチラゼの必要性を調べる

主要な成果:

OSK遺伝子の発現は年老いた網膜細胞における若々しいDNAメチル化パターンとトランスクリプトームを回復させた.
損傷後の軸索再生を促し,緑内障と老いたマウスの視力喪失を逆転させた.
OSKの再生効果と視力を回復させる効果は,DNAデメチラゼTET1とTET2に依存していた.

結論:

哺乳類の組織は DNA メチル化によって部分的にコード化された青春期の表遺伝子情報を保持しています
このエピジェネティック情報は遺伝子再プログラムによって得られ,組織機能を改善し,体内の再生を促進します.
エピジェネティックメカニズムをターゲットにすることで老化による衰弱と闘い再生能力の強化の戦略が生まれます

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