Single-cell transcriptomics reveals e-cigarette vapor-induced airway epithelial remodeling and injury.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2024-09-28 DOI:10.1186/s12931-024-02962-4

Weitao Cao, Jia Li, Li Che, Ruixue Yang, Zehong Wu, Guoping Hu, Weifeng Zou, Zehang Zhao, Yumin Zhou, Xingtao Jiang, Tiejun Zhang, Wenguang Yin, Pixin Ran

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Abstract

Background: In recent years, e-cigarettes have been used as alternatives among adult smokers. However, the impact of e-cigarette use on human bronchial epithelial (HBE) cells remains controversial.

Methods: We collected primary HBE cells of healthy nonsmokers and chronic obstructive pulmonary disease (COPD) smokers, and analyzed the impact of e- cigarette vapor extract (ECE) or cigarette smoke extract (CSE) on HBE cell differentiation and injury by single-cell RNA sequencing, immunostaining, HE staining, qPCR and ELISA. We obtained serum and sputum from healthy non- smokers, smokers and e-cigarette users, and analyzed cell injury markers and mucin proteins.

Results: ECE treatment led to a distinct differentiation program of ciliated cells and unique patterns of their cell-cell communications compared with CSE. ECE treatment caused increased Notch signaling strength in a ciliated cell subpopulation, and HBE cell remodeling and injury including hypoplasia of ciliated cells and club cells, and shorter cilia. ECE-induced hypoplasia of ciliated cells and shorter cilia were ameliorated by the Notch signaling inhibition.

Conclusions: This study reveals distinct characteristics in e-cigarette vapor-induced airway epithelial remodeling, pointing to Notch signaling pathway as a potential targeted intervention for e-cigarette vapor-caused ciliated cell differentiation defects and cilia injury. In addition, a decrease in SCGB1A1 proteins is associated with e- cigarette users, indicating a potential lung injury marker for e-cigarette users.

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单细胞转录组学揭示了电子烟蒸汽诱导的气道上皮重塑和损伤。

背景：近年来，电子烟已成为成年吸烟者的替代品。然而，使用电子烟对人类支气管上皮细胞（HBE）的影响仍存在争议：我们收集了健康非吸烟者和慢性阻塞性肺病（COPD）吸烟者的原代 HBE 细胞，并通过单细胞 RNA 测序、免疫染色、HE 染色、qPCR 和 ELISA 分析了电子烟蒸汽提取物（ECE）或香烟烟雾提取物（CSE）对 HBE 细胞分化和损伤的影响。我们采集了健康非吸烟者、吸烟者和电子烟使用者的血清和痰液，分析了细胞损伤标记物和粘蛋白：结果：与CSE相比，ECE处理导致了纤毛细胞的独特分化程序及其独特的细胞间通讯模式。ECE 处理会导致纤毛细胞亚群的 Notch 信号强度增加，并导致 HBE 细胞重塑和损伤，包括纤毛细胞和棒状细胞减少以及纤毛变短。Notch信号抑制可改善ECE诱导的纤毛细胞减少和纤毛变短：这项研究揭示了电子烟蒸汽诱导的气道上皮重塑的独特特征，指出Notch信号通路是治疗电子烟蒸汽导致的纤毛细胞分化缺陷和纤毛损伤的潜在靶向干预措施。此外，SCGB1A1 蛋白的减少与电子烟使用者有关，这表明电子烟使用者有可能成为肺损伤标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.