Xist RNAは,マウスの血液がんの強力な抑制剤です
Eda Yildirim1, James E Kirby, Diane E Brown
1Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell
|February 19, 2013
まとめ
マウスのXistRNA喪失によるX染色体不活性化 (XCI) 障害は,骨髄増殖性腫瘍および骨髄分裂症候群を含む攻撃的な血液がんを引き起こす. この研究は,X染色体の機能とがん抑制を因果的に関連づけています.
科学分野:
- 遺伝学 遺伝学とは
- がん生物学 がん生物学
- 哺乳類の発達について
背景:
- X染色体アヌプロイド症はヒトのがんと関連しているが,因果関係は未だ証明されていない.
- 哺乳類のX染色体不活性化 (XCI) は,XistRNAに依存して,性別間の遺伝子発現を均等にします.
研究 の 目的:
- 血液形成系内のがん発症におけるXist RNAの因果的役割を調査する.
- Xist RNAががんを活力的に抑制するかどうかを in vivoで判断する.
主な方法:
- Xist遺伝子の削除は,マウスの血液細胞区画に特化した.
- 造血幹細胞 (HSC) の機能,成熟,および年齢による変化の分析.
- 疾患の起源を評価するための血液形成性幹細胞再構成実験.
主要な成果:
- Xist欠陥の雌マウスは,100%の浸透率で攻撃的な混合骨髄増殖性腫瘍/骨髄分裂症候群 (MPN/MDS) を発症した.
- 疾患には,原発性骨髄膜症,白血病,ヒスティオサイト性肉腫,および血管炎が含まれていました.
- Xist欠乏性HSCは,異常な成熟と年齢による衰退を示し,MPN/MDSと血液形成細胞から発生したミエロ繊維症を示した.
結論:
- XistRNAは,X染色体の不活性化を維持するために不可欠であり,がんの発症を積極的に抑制します.
- Xistの喪失は,Xの活性化とゲノム全体の変異につながり,X染色体とマウスの癌の発症を因果的に結びつける.
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