霊長類特異的な内生レトロウイルス駆動の転写は,ナイヴのような幹細胞を定義します
Jichang Wang1, Gangcai Xie2, Manvendra Singh1
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Nature
|October 16, 2014
まとめ
研究者らは,素朴な性質を示すヒト幹細胞のサブ集団を特定した. これらの細胞は,霊長類特異的なレトロウイルスであるHERVHと,多能性を調節する新しい転写回路に関連しています.
科学分野:
- 幹細胞生物学 幹細胞生物学とは
- ゲノミクスゲノミクスとは
- 発達生物学 発達生物学とは
背景:
- ネイブ胚性幹細胞 (ESC) は,研究と治療において極めて重要な幅広い発達可能性を秘めています.
- 人間の素朴なESCを隔離することは困難である;現在の方法は,原始化された人間のESCまたは誘導された多能幹細胞 (hiPSC) から素朴な細胞のような細胞の人工生成を伴う.
研究 の 目的:
- 人間のESCとhiPSCの培養の中でナイヴのような細胞の自然に発生するサブ集団を特定し,特徴づけること.
- プライマットに特異的な内生レトロウイルス,特にHERVHが,これらの素朴な細胞の多能性を調節する役割を調査する.
主な方法:
- 人間のESCとhiPSC文化のサブ集団の分析.
- 細胞の遺伝的タグ付け.
- 転写プロファイリングは,HERVHおよびLBP9.9のような関連因子に焦点を当てて行われます.
- 重要な遺伝要素 (LBP9,HERVH) の破壊を含む機能的研究.
主要な成果:
- hESCsとhiPSCsのサブ集団は,ネイブ幹細胞の性質を自然に表しています.
- 高い HERVH トランスクリプションは,これらの素朴な細胞のような細胞の特徴です.
- HERVH要素は,LBP9を含むナイブ多能性因子の結合部位として機能し,ユニークなトランスクリプトを駆動する.
- LBP9,HERVH,または由来トランスクリプトの障害は,自己更新能力を損なう.
結論:
- HERVH発現は,素朴な人間のESCの決定的な特徴です.
- HERVHとLBP9を含む新種の霊長類特異的転写回路は,多能性と自己再生を調節する.
- この発見は,ヒトの幹細胞における多能性の調節に関する新しい洞察を提供します.
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