Modifications of lipid pathways restrict SARS-CoV-2 propagation in human induced pluripotent stem cell-derived 3D airway organoids

Ping-Hsing Tsai,Jun-Ren Sun,Yueh Chien, Man Sheung Chan, Winnie Khor,Hsin-Chou Yang,Chih-Heng Huang,Chia-Ni Hsiung, Teh-Yang Hwa,Yi-Ying Lin, Chih-Ling Yeh,Mong-Lien Wang,Yi-Ping Yang,Yuh-Min Chen,Fu-Ting Tsai,Meng-Shiue Lee, Yun-Hsiang Cheng,Shan-Ko Tsai,Ping-Cheng Liu,Shih-Jie Chou

Journal of Advanced Research（2023）

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摘要

Human iPSC-derived airway organoids (iPSC-AOs) exhibit cellular heterogenicity resembling the human native airway. Bioinformatics analysis revealed a robust dysregulation in inflammation, lipid-metabolism pathway, and alternative splicing in SARS-CoV-2 infected airway organoids. Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2), leading to the reduction of SARS-CoV-2 entry and replication.

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关键词

Severe acute respiratory syndrome coronavirus 2,Induced pluripotent stem cell,Airway organoid,Angiotensin-converting enzyme 2,Single cell RNA-sequencing

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