APC腫瘍抑制剤とセンターソームによる非対称性幹細胞分裂の指向

Yukiko M Yamashita¹, D Leanne Jones, Margaret T Fuller

¹Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.

Science (New York, N.Y.)

|September 13, 2003

まとめ

ドロソフィラの雄性幹細胞は,内部メカニズムを使って非対称的に分裂する. これは,1つの子細胞が幹細胞プールを更新し,もう1つの子細胞が分化し,幹細胞のバランスを維持することを保証します.

科学分野:

発達生物学発達生物学について
幹細胞生物学幹細胞生物学
細胞メカニズム細胞メカニズム

背景:

幹細胞の自己再生は,マイクロ環境 (ニッチ) によって調節されます.
幹細胞の自己再生と分化をバランスさせるメカニズムは不明である.
幹細胞のニッチ相互作用を理解することは,再生医療にとって極めて重要です.

研究の目的:

ニッチと幹細胞の自己再生/差別化のバランスの間の関係を調査する.
ドロソフィラの雄性生殖系幹細胞における非対称的な幹細胞分裂を制御する細胞内メカニズムを解明する.

主な方法:

Drosophila melanogasterをモデル生物として利用しました.
センターソーム機能を含む細胞内メカニズムを研究した.
ニッチ相互作用とスパインドル指向におけるAdenomatous Polyposis Coli (APC) 腫瘍抑制タンパク質の役割を調べました.

主要な成果:

分裂するドロソフィラの雄性生殖系幹細胞は,ニッチに垂直してミトスフィンドルを方向づけます.
セントロソーム機能と皮質局所化されたAPCタンパク質は,スパインドル指向の鍵です.
この方向性は,非対称な細胞分裂を保証し,ある子細胞の幹細胞同一性を維持し,他の子細胞の分化を開始します.

結論:

セントロソーム機能とAPCタンパク質を含む細胞内メカニズムは,非対称的な幹細胞分裂に不可欠です.
ニッチに対する適切なスパインドル指向は,幹細胞ホメオスタシスを維持するために不可欠です.
発見は,発達生物学と疾患に関連する基本的な幹細胞の調節に関する洞察を提供します.

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