Notch-Collagen V-CALCRによる相互信号は,筋肉幹細胞をそのニッチに保持する
Meryem B Baghdadi1,2,3, David Castel4,5, Léo Machado6
1Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris, France.
Nature
|May 26, 2018
まとめ
成人筋幹細胞は,ノッチ-コラーゲンV-カルチトニン受容体の信号伝達経路によって調節される細胞外マトリックスコラーゲンを生成することによって静止状態を維持する.
科学分野:
- 筋肉幹細胞生物学
- 細胞外マトリックス
- セルラー信号
背景:
- 幹細胞のニッチは,幹細胞の維持に不可欠であり,細胞と非細胞の成分を含みます.
- ノッチ信号は幹細胞の静止を調節しますが,ニッチを維持する特定の分子とその源はほとんど知られていません.
研究 の 目的:
- 筋肉の衛星幹細胞が静止状態を維持する細胞自律的メカニズムを調査する.
- 幹細胞のニッチの新しい構成要素とその規制経路を特定する.
主な方法:
- NOTCH1/RBPJの結合部位を特定するために,染色体免疫降水とシーケンシング (ChIP-seq) が続く.
- 衛星細胞機能におけるコラーゲンV (COLV) の役割を評価するための条件付きの遺伝子削除.
- レスキュー効果を評価するために,カルシトニン誘導体の全身投与.
主要な成果:
- 大人の筋肉の衛星細胞は,細胞自律的な方法で,COLVを含む細胞外マトリックスコラーゲンを産生する.
- NOTCH1/RBPJはコラーゲン遺伝子発現を直接制御する.
- COLVは衛星細胞の静止状態を維持するために不可欠であり,その枯渇は細胞サイクルへの入り込みと幹細胞プール減少につながる.
- COLVは,カルシトニン受容体を通して衛星細胞と相互作用し,局所リガンドとして作用する.
結論:
- 新しいノッチ-COLV-カルシトニン受容体シグナリングカスケードは,筋肉の衛星幹細胞の静止細胞を自律的に維持する.
- この経路は,幹細胞のニッチ内の相互相互作用を強調しています.
- 他の幹細胞群の維持にも同様のメカニズムが関与している可能性があります.
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