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人体呼吸道上皮质对SARS-CoV-2的体外反应的转录组景观

Said Assou¹, Engi Ahmed^1,2,3, Lisa Morichon^1,4

¹IRMB, University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France.

International journal of molecular sciences

|August 12, 2023

概括

感染SARS-CoV-2的气道-液体接口培养物显示干扰素和炎症基因表达的增加. 这些模型揭示了呼吸道上皮损伤和改变的细胞通信,有助于COVID-19治疗的发展.

科学领域:

* 呼吸道病毒感染研究
*人类呼吸道上皮细胞生物学
* 转录学和单细胞RNA测序

背景情况:

* 气道-液体接口 (ALI) 和诱导的ALI (iALI) 培养物生理上模仿了人体支气管上皮.
* 这些模型对于研究呼吸道病毒感染,包括SARS-CoV-2至关重要.
* 了解基因表达水平上的宿主反应对于开发有效治疗方法至关重要.

研究的目的:

* 在SARS-CoV-2感染后研究ALI和iALI模型中的基因表达特征.
* 确定关键的宿主基因和参与呼吸道上皮质对SARS-CoV-2的反应的途径.
* 评估ALI/iALI模型在了解COVID-19病变发生过程中的有用性.

主要方法:

*利用来自人类气道培养的批量和单细胞转录组数据集 (ALI和iALI模型).
*ALI和iALI模型感染严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2).
*在感染后的第四天对基因表达变化的分析.

主要成果:

* 在感染的呼吸道培养物中,干扰素刺激基因 (例如IFI44,IFIT1,MX1) 和炎症基因 (例如NFKBIA,CXCL10) 的显著上调.
*观察到细胞外基因基因的变化 (例如,ITGB6,GJA1).
*单细胞RNA测序揭示了呼吸道上皮的损伤,特别是毛细胞,以及细胞间通信/粘附基因的放松调节.

结论:

*ALI/iALI模型有效地重复了人类呼吸道上皮质对SARS-CoV-2感染的反应.
*观察到的基因表达变化突出显示了先天免疫反应和上皮损伤的激活.
*这些模型是推动COVID-19治疗药物的发展的宝贵工具.

关键词:

这是SARS-CoV-2的签名.呼吸道在体外模型中的体外模型.iPS 细胞细胞 iPS 细胞转录组分析转录组分析

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