Single-cell Transcriptome Analysis Reveals an Anomalous Epithelial Variation and Ectopic Inflammatory Response in Chronic Obstructive Pulmonary Disease
Single-cell Transcriptome Analysis Reveals an Anomalous Epithelial Variation and Ectopic Inflammatory Response in Chronic Obstructive Pulmonary Disease
Abstract Chronic obstructive pulmonary disease (COPD) is a progressive disease that obstructs the airflow from the lungs, and tobacco smoking is the major cause of COPD. Here, we applied single-cell RNA sequencing to analyze COPD pathogenesis in COPD patients, non-COPD smokers and never-smokers and investigated the disease progression at single-cell resolution. By single-cell transcriptome analysis, COPD was characterized by shifts in the stromal, immune system and epithelial cell compositions. While epithelial components in never-smokers were relatively uniform, the smoker groups presented with extensive heterogeneity in epithelial cells, particularly in the alveolar type II (AT2) lineages. We identified a subpopulation of AT2 epithelial cells that emerged in smokers, such as COPD patients, and specifically expressed a series of chemokines and PD-L1. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred increased intercellular networks of inflammatory AT2 cells with immune and stromal cell populations. Thus, our analysis reveals a unique cellular differentiation pathway and function underlying the biological and clinical characteristics of COPD pathogenesis.
Araya Jun、Yamamoto Yusuke、Okamoto Koji、Fujita Yu、Kadota Tsukasa、Ohtsuka Takashi、Kuwano Kazuyoshi、Shimomura Iwao、Mori Yutaro、Watanabe Naoaki、Nakayama Jun
Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cellular Signaling, National Cancer Center Research InstituteDivision of Cancer Differentiation, National Cancer Center Research InstituteDivision of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of MedicineDivision of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of MedicineDivision of Thoracic Surgery, Department of Surgery, The Jikei University School of MedicineDivision of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cellular Signaling, National Cancer Center Research InstituteDivision of Cancer Differentiation, National Cancer Center Research InstituteDivision of Cellular Signaling, National Cancer Center Research Institute||Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cellular Signaling, National Cancer Center Research Institute
基础医学细胞生物学分子生物学
Araya Jun,Yamamoto Yusuke,Okamoto Koji,Fujita Yu,Kadota Tsukasa,Ohtsuka Takashi,Kuwano Kazuyoshi,Shimomura Iwao,Mori Yutaro,Watanabe Naoaki,Nakayama Jun.Single-cell Transcriptome Analysis Reveals an Anomalous Epithelial Variation and Ectopic Inflammatory Response in Chronic Obstructive Pulmonary Disease[EB/OL].(2025-03-28)[2025-04-26].https://www.medrxiv.org/content/10.1101/2020.12.03.20242412.点此复制
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