ヒトの遠端肺臓器官における原始体識別とSARS-CoV-2感染
Ameen A Salahudeen1,2, Shannon S Choi1, Arjun Rustagi3
1Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|November 25, 2020
まとめ
研究者らは新しい 3D 遠肺器官モデルを開発した. このシステムは,COVID-19のような肺疾患の研究を容易にし,クラブ細胞をSARS-CoV-2の標的として識別します.
科学分野:
- 肺医学
- 細胞生物学
- 感染症
背景:
- 遠い肺のガス交換機能は 極めて重要です
- COVID-19のような肺疾患を調査するには 先進的な実験室内モデルが必要です
- 現在のモデルでは 遠隔肺の病態を完全に再現する複雑性が欠けている.
研究 の 目的:
- 長期にわたるフィーダーフリー3Dヒト遠肺器官培養システムを開発する.
- 遠い肺内の原始細胞の異質性を特徴付ける.
- SARS-CoV-2を含む遠隔肺感染症の研究モデルを確立する.
主な方法:
- 成人ヒトのアルベオラ上皮質II型 (AT2) とKRT5+基底細胞から遠端肺器官生成
- 化学的に定義された長期の養殖条件.
- 単細胞RNA配列解析と機能分析により,細胞集団と感染感受性を分析する.
主要な成果:
- 機能的な遠肺器官が発達し,AT1,クラブ,および毛皮細胞に微分化することができる.
- 塩基細胞 (ITGA6+ITGB4+ミトーシス細胞) の独特のサブポピュレーションを特定し,クローン生成の可能性が高い.
- SARS-CoV-2感染をモデル化するためにアピカルアウトオーガノイドを作成し,標的としてクラブ細胞を明らかにし,AT2細胞の感受性を確認しました.
結論:
- 多機能で長期にわたるヒトの遠端肺器官系を確立した.
- 基礎原始細胞内の機能的異質性が実証されている.
- COVID-19肺炎を含むヒトの遠隔肺感染症を研究するための簡単な実験室内モデルを提供した.
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