在人类远端肺器官中发现原始体和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
概括
研究人员开发了一种新的3D人类远端肺器官模型. 该系统有助于研究COVID-19等肺部疾病,并识别 SARS-CoV-2 的目标.
科学领域:
- 肺部医学
- 细胞生物学
- 传染性疾病
背景情况:
- 远距离肺部的气体交换功能非常重要.
- 调查COVID-19等肺部疾病需要先进的体外模型.
- 目前的模型缺乏复杂性,无法完全复制远端肺病理.
研究的目的:
- 开发一个长期的,无料的3D人类远端肺器官培养系统.
- 描述远端肺中的原始细胞异质性.
- 建立一个研究远端肺部感染的模型,包括SARS-CoV-2.
主要方法:
- 从成年人膜上皮类型II (AT2) 和KRT5+基底细胞生成远端肺器官.
- 长期,无料,化学定义的培养条件.
- 单细胞RNA测序和功能测定以分析细胞群和感染易感性.
主要成果:
- 有能力分化为AT1细胞和状细胞的功能性远端肺器官.
- 鉴定出具有高克隆性潜力的基底细胞 (ITGA6+ITGB4+细胞) 的独特亚群.
- 为模拟SARS-CoV-2感染而创建的尖端器官,揭示了俱乐部细胞作为目标,并证实了AT2细胞的易感性.
结论:
- 建立了一个多功能,长期无料的人类远端肺器官系统.
- 在基底细胞中证明功能异质性.
- 为研究包括COVID-19肺炎在内的人类远距离肺部感染提供了一个简单的体外模型.
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