単細胞のWntシグナルニッチは,アルベオラ型2細胞の幹性を維持する
Ahmad N Nabhan1,2, Douglas G Brownfield1,2, Pehr B Harbury1
1Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Science (New York, N.Y.)
|February 9, 2018
まとめ
肺幹細胞 (AT2s) は,維持のために線維細胞が分泌するWnt信号に依存しています. このWntニッチの破壊は幹細胞の喪失を引き起こし,ガス交換細胞 (AT1) に分化を促進する.
科学分野:
- 肺の生物学
- 幹細胞生物学
- セル・シグナル
背景:
- アルベオルは肺のガス交換単位で,アルベオラ型1 (AT1) とAT2細胞で覆われています.
- AT2細胞は表面活性物質を分泌し,希少なAT2細胞はアルベオラの幹細胞として作用する.
研究 の 目的:
- AT2肺幹細胞の維持におけるWnt信号伝達の役割を調査する.
- AT2幹細胞の維持と分化メカニズムを解明する.
主な方法:
- AT2幹細胞と周囲の線維芽細胞におけるWnt信号の分析
- Wnt分泌とシグナル伝達経路の実験操作
- Wnt経路の調節後の幹細胞集団と細胞運命を評価する.
主要な成果:
- AT2幹細胞はWntシグナル伝達が活発であり,しばしばWnt発現する線維芽細胞の近くに位置する.
- Wntの分泌を阻害すると,AT2幹細胞が枯渇する.
- Wntシグナリングを維持すると,AT2のAT1細胞への変異が防止され,それを廃止すると変異が促進される.
- 肺損傷はAT2細胞の自己決定性Wnt信号を誘発し,原始細胞群を拡大する.
結論:
- 個々のAT2幹細胞は,隣接する線維芽細胞の信号によって維持される.
- 傷は Wntの自己決定信号を誘発し 暫定的な祖先の拡大を促します
- このニッチメカニズムは肺のガス交換表面を維持するために不可欠であり,癌に関与しています.
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