進化的に保存された上皮原体による肺膜の再生
William J Zacharias1,2, David B Frank2,3,4, Jarod A Zepp1,2
1Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature
|March 1, 2018
まとめ
研究者らは肺に特異なアルベオラ上皮原生細胞 (AEP) 系統を発見した. これらのAEPは,損傷後の肺組織の再生に不可欠であり,肺再生療法のための新しいターゲットを提供します.
科学分野:
- 肺医学
- 再生生物学
- 細胞生物学
背景:
- 損傷後の臓器の恒常性には 機能的な組織再生が不可欠です
- 肺のような静止している臓器は 再生のために 選択的な原始細胞に依存しています
- 肺の修復メカニズムを理解するには 特定の原始細胞を特定することが重要です
研究 の 目的:
- 再生を担当する遠肺のプロジェニータ細胞を特定し,特徴づけること.
- Wnt反応性アルベオラ上皮原細胞 (AEP) の肺修復における役割を調査する.
- ヒトのAEPを分離して 再生戦略に使用できるかどうかを判断する.
主な方法:
- アルベオラ上皮原細胞のトランスクリプトミックとエピジェノミックプロファイリング.
- 急性肺損傷後のAEP系統の拡大に関するin vivo研究.
- 3Dオーガノイドモデルを用いたヒトAEPの分離と機能評価
- WntとFgf信号経路の関与の分析
主要な成果:
- Wnt反応性アルベオラ上皮原体 (AEP) 系統が2型アルベオラ細胞内で確認された.
- AEPはホメオスタシス中に安定しますが,損傷後の膜上皮質を再生するために著しく拡張します.
- AEPは,WntとFgfの信号に反応する独特の分子と機能のプロファイルを持っています.
- 人間のAEPはTM4SF1マーカーを使用して分離され,オルガノイドの再生能力が実証されました.
結論:
- AEPの系統は,遠端肺の主要な選択的前駆細胞を表しています.
- この系統は進化的に保存され 肺の再生に重要な役割を果たしています
- AEPをターゲットにすることで 人間の肺再生戦略に 新しい希望が生まれます
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