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動脈化には,細胞の成長を時宜抑制することが必要です
Wen Luo1, Irene Garcia-Gonzalez1, Macarena Fernández-Chacón1
1Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Nature
|December 10, 2020
まとめ
血管の発達は VEGFやNotchのような信号伝達経路に依存しています 動脈プログラムを直接誘導するのではなく 細胞サイクルと代謝を抑制することが 動脈形成の鍵です
科学分野:
- 発達生物学
- 血管生物学
- 細胞シグナリング
背景:
- 動脈の形成は 保存された遺伝プログラムと 血流の増加に関連しています
- 血管内皮成長因子 (VEGF) とノッチシグナル伝達経路は,初期動脈の特異化にとって極めて重要です.
- 細胞増殖と分化における これらの経路の正確な役割を理解することは不可欠です
研究 の 目的:
- 細胞増殖,動脈静脈分化,動員における VEGF と Notch 信号伝達の機能を調査する.
- これらの経路が動脈と静脈形成に影響を与えるメカニズムを決定する.
- 信号伝達経路,細胞サイクル,代謝,動脈発達の関係を明らかにする.
主な方法:
- VEGFとNotchのシグナリングを調節するために誘導可能な遺伝子モザイクを使用しました.
- 遺伝子発現の変化を分析するためにトランスクリプトミクスを用いた.
- 内皮細胞の運命を追跡するために モザイク系統追跡研究を行った.
主要な成果:
- 高VEGFまたはNotchシグナリングは,内皮細胞を動員して動脈を形成させるが,その運命を事前に決定しない.
- VEGFとNotchのシグナル伝達が増加すると,MYCに依存する細胞サイクルと毛細血管の代謝活動が抑制され,動脈の組み込みが促進されます.
- ノッチ-RBPJ機能の喪失は動脈形成を阻害し,MYCを抑制することで救出することができます.
結論:
- 動脈の発達は,ノッチ依存性動脈プログラムによる直接的誘導によるものではありません.
- 動脈の特異性は,内皮細胞サイクル進行と代謝の適切な抑制に依存する.
- この抑制は動脈の動員と分化に先行し,血管の発達における新しいメカニズムを強調しています.
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