細胞内pH制御 WNT 胚子における糖分解の下流
Masayuki Oginuma1,2,3, Yukiko Harima1,2, Oscar A Tarazona1,2
1Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nature
|June 26, 2020
まとめ
胚の尾芽細胞は,WNT信号を調節し,体の伸びを促すために,がん細胞に似た有酸素糖解を用いる. この代謝過程は 細胞の発達過程に影響を与えます
科学分野:
- 発達生物学
- 細胞の代謝
- 癌 生物学
背景:
- 脊椎動物の胚の形成は,尾の芽からの後部組織添加に依存しています.
- 尾芽細胞は,がん細胞に似た高有酸素糖分解 (ウォーバーグ効果) を表している.
- 線維細胞成長因子による糖分解は,尾芽のWNT信号伝達に影響する.
研究 の 目的:
- 尾芽内のWNTシグナリングの調節における糖解の役割を調査する.
- 代謝状態が胚の発達に 細胞の運命をどう影響するのかを理解する
- 発達の代謝プログラムと癌細胞代謝の関連性を調べる
主な方法:
- 鶏の胚を in vivo 研究に使用した.
- 誘発性多能性幹細胞からヒトの尾の芽のような細胞を in vitro で分化した.
- 分析されたpHグラディエント,モノカルボキシレートシンポーターによる乳酸エクストルーション,およびβ-カテニンのアセチル化.
主要な成果:
- 尾芽細胞の逆のpHグラデント (細胞外pHが細胞内pHより低い) が観察され,がん細胞に似ている.
- 乳酸と陽子の流出を促進し,細胞内pHを増加させることが示された.
- 細胞内pHが上昇すると,非酵素β-カテニンのアセチル化が促進され,メソダーマの運命を促進することが示された.
結論:
- グライコリシスは,細胞内pHとβ-カテニンのアセチル化を調節することによって,尾芽細胞におけるWNTシグナリングを調節する.
- この代謝経路は,パラキシアル・メソデルマを特定し,軸の伸びを可能にするために極めて重要です.
- この発見は,がん細胞が発達代謝プログラムを再活性化することを示唆しています.
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