RESTは,胚性幹細胞の自己再生と多能性を維持する
Sanjay K Singh1, Mohamedi N Kagalwala, Jan Parker-Thornburg
1Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Nature
|March 26, 2008
まとめ
神経抑制剤RESTは,マイクロRNA-21を抑制することによってマウスの胚性幹細胞の自己再生と多能性を維持する. RESTの喪失は差別化につながり,RESTの追加は自己再生と主要な多能性要因を促進します.
科学分野:
- 幹細胞生物学 幹細胞生物学
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
背景:
- ネズミの胚性幹細胞 (ESC) は,高いレベルの神経抑制物質REST (RE1を静止する転写因子) を発現する.
- ESCの自己更新と多能性におけるRESTの正確な機能は,まだ完全に理解されていません.
研究 の 目的:
- マウスのESCにおける自己再生と多能性の維持におけるRESTの役割を明らかにする.
- RESTがESCの運命決定に影響を与える規制メカニズムを調査する.
主な方法:
- 自己再生におけるREST発現レベルと,差異化しているESC (胚体) の分析.
- ネズミのESCおよび胚体におけるRESTレベル (異卵性削除,siRNAノックダウン,外因的添加) の遺伝子操作.
- 自己更新マーカー (Oct4,Nanog,Sox2,c-Myc) と系統特有のマーカーの評価.
- miRNA遺伝子上のREST結合部位を特定するためにクロマチン免疫プレシピテーション.
- miRNA発現の定量化,特にmiR-21について.
主要な成果:
- RESTの発現は,微分化胚体と比較して,自己再生するESCにおいて著しく高い.
- ESCにおけるREST機能の喪失は,自己更新の喪失と複数の系統マーカーの誘導につながる.
- 外因的なRESTの追加は,分化細胞の自己再生を救出し,多能性マーカーを維持します.
- RESTは,自己更新調節体を標的とするmiR-21を含むmiRNAのクロマチンに直接結合する.
- miR-21は,Oct4,Nanog,Sox2,c-Mycをダウンレギュレーションすることによって,ESCの自己更新を抑制する.
結論:
- RESTはマウスのESCの自己再生と多能性を維持するための重要な要因です.
- RESTは,多能性遺伝子の重要な負の調節体であるmiR-21を抑制することで,その機能を部分的に果たします.
- RESTは,ESCの運命を支配する規制ネットワークの不可欠な構成要素です.
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