腸内密室を支えるWntsの重要な源は,亜皮質テロサイトです
Michal Shoshkes-Carmel1, Yue J Wang1, Kirk J Wangensteen1
1Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|May 4, 2018
まとめ
副皮質テロ細胞は,腸の幹細胞増殖と上皮質再生に不可欠なWntタンパク質を生成する重要なニッチ細胞です. 機能不全でWnt信号が停止し 組織再生が妨げられます
科学分野:
- 胃腸内科
- 幹細胞生物学
- セルラー・シグナル
背景:
- 腸内皮質のような素早く自己再生する組織は 幹細胞と前身細胞に依存しています
- これらの幹細胞は 増殖と自己再生のために 局所的なニッチ細胞からの信号を必要とします
- 特定のニッチ細胞と腸の幹細胞を調節する信号は,まだ完全に理解されていません.
研究 の 目的:
- 腸の幹細胞に重要な信号を送る 特定のニッチ細胞を特定する
- これらのニッチ細胞がWntシグナル伝達と腸内上皮質再生を調節する役割を明らかにする.
主な方法:
- FOXL1+テロサイトにおけるポルクシン (Porcn) の条件付き遺伝子切除によるマウスモデルを使用した.
- FOXL1の発現を胃腸全域でプレクサスを形成する亜皮質テロサイトで調査した.
- 分析されたWntシグナル伝達,幹細胞とトランジット増強細胞の増殖,そしてテロサイト特異的な遺伝子除去後の上皮細胞の再生.
主要な成果:
- FOXL1+亜皮質テロ細胞は腸の幹細胞のためのWntタンパク質の主要な源として特定されました.
- 局所的な経路の活性化のために,テロサイトがWntリガンドと阻害剤の産生を区分することを示した.
- FOXL1+テロサイトにおけるPorcnの除去により,Wntのシグナル伝達が急速に停止し,幹細胞の増殖が失われ,上皮の再生が低下することが示された.
結論:
- FOXL1+テロ細胞は,Wntタンパク質の生産を通じて腸の幹細胞機能を調節する重要なニッチ細胞です.
- これらのテロ細胞は腸内皮質のホメオスタシスと再生を維持する上で重要な役割を果たします.
- テロサイト由来Wntシグナリングをターゲットにすることは,腸の障害に対する潜在的な治療戦略です.
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