Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation

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作   者：

Bankoti, Kamakshi;  Wang, Wei;  Amonkar, Gaurang M.;  Xiong, Linjie;  Shui, Jessica E.;  Zhao, Caiqi;  Van, Eric;  Mwase, Chimwemwe;  Park, Jin-Ah;  Mou, Hongmei;  Fang, Yinshan;  Que, Jianwen;  Bai, Yan;  Lerou, Paul H.;  Ai, Xingbin; 

作者机构：

Med CtrVanderbilt University Department of Biomedical Informatics Vanderbilt University Dept Biomed; 

关键词：

COVID-19;  mucociliary differentiation;  EPITHELIUM;  airway basal cells;  inflammation;  REGENERATION;  INFLAMMATORY MEMORY;  epithelial regeneration; 

期刊名称：

American journal of respiratory cell and molecular biology.

i s s n：

1044-1549

年卷期：

2024 年 70 卷 1 期

页   码：

26-38

页   码：

摘   要：

Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent the biosafety concerns of live-cell derivation. We show that BSCs derived from the TAs of control patients are bona fide bronchial BSCs. TA BSCs from patients with COVID-19 tested negative for severe acute respiratory syndrome coronavirus 2 RNA; however, these so-termed COVID-19-exposed BSCs in vitro resemble a predominant BSC subpopulation uniquely present in patients with COVID-19, manifested by a proinflammatory gene signature and STAT3 hyperactivation. Furthermore, the sustained STAT3 hyperactivation drives goblet cell differentiation of COVID-19-exposed BSCs in an air-liquid interface. Last, these phenotypes of COVID-19-exposed BSCs can be induced in control BSCs by cytokine cocktail pretreatment. Taken together, acute inflammation in COVID-19 exerts a long-term impact on mucociliary differentiation of BSCs.