Yuling Han, Dongliang Leng, Tuo Zhang, Jian Ge, Yinshan Fang, Tiankun Lu, Xue Dong, Manoj S Nair, Neranjan de Silva, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Anjali Saqi, Hanina Hibshoosh, Zihe Meng, Jenny Z Xiang, Chendong Pan, Yanjie Sun, David D Ho, Todd Evans, Jie Liu, Liuliu Yang, Jianwen Que, Shuibing Chen
{"title":"研究SARS-CoV-2感染后巨噬细胞介导的肺细胞衰老的人免疫-肺类器官模型","authors":"Yuling Han, Dongliang Leng, Tuo Zhang, Jian Ge, Yinshan Fang, Tiankun Lu, Xue Dong, Manoj S Nair, Neranjan de Silva, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Anjali Saqi, Hanina Hibshoosh, Zihe Meng, Jenny Z Xiang, Chendong Pan, Yanjie Sun, David D Ho, Todd Evans, Jie Liu, Liuliu Yang, Jianwen Que, Shuibing Chen","doi":"10.1002/advs.202503932","DOIUrl":null,"url":null,"abstract":"<p><p>While COVID-19 affects multiple organ systems, the human respiratory system is the primary viral target and main site for disease progression. In this study, spatial transcriptional assays (NanoString CosMx) are utilized to analyze both explant and autopsy samples from non-COVID and COVID-19 lungs, identifying the activation of proinflammatory macrophages in COVID-19 explants. It is further developed immuno-lung organoids comprising hPSC-derived alveolar and airway organoids co-cultured with macrophages to investigate the impact and underlying mechanisms of macrophage-mediated lung damage following SARS-CoV-2 infection. The findings demonstrate that proinflammatory macrophages induce lung cell senescence through the THBS1-(ITGA3+ITGB1) signaling axis, a mechanism further validated using spatial transcriptomics. This study not only establishes physiologically relevant immuno-lung organoid models for modeling macrophage-mediated tissue damage, but also identifies a previous unrecognized role of the THBS1-(ITGA3+ITGB1) pathway in driving lung cell senescence during infectious disease.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e03932"},"PeriodicalIF":14.3000,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Human Immuno-Lung Organoid Model to Study Macrophage-Mediated Lung Cell Senescence Upon SARS-CoV-2 Infection.\",\"authors\":\"Yuling Han, Dongliang Leng, Tuo Zhang, Jian Ge, Yinshan Fang, Tiankun Lu, Xue Dong, Manoj S Nair, Neranjan de Silva, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Anjali Saqi, Hanina Hibshoosh, Zihe Meng, Jenny Z Xiang, Chendong Pan, Yanjie Sun, David D Ho, Todd Evans, Jie Liu, Liuliu Yang, Jianwen Que, Shuibing Chen\",\"doi\":\"10.1002/advs.202503932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>While COVID-19 affects multiple organ systems, the human respiratory system is the primary viral target and main site for disease progression. In this study, spatial transcriptional assays (NanoString CosMx) are utilized to analyze both explant and autopsy samples from non-COVID and COVID-19 lungs, identifying the activation of proinflammatory macrophages in COVID-19 explants. It is further developed immuno-lung organoids comprising hPSC-derived alveolar and airway organoids co-cultured with macrophages to investigate the impact and underlying mechanisms of macrophage-mediated lung damage following SARS-CoV-2 infection. The findings demonstrate that proinflammatory macrophages induce lung cell senescence through the THBS1-(ITGA3+ITGB1) signaling axis, a mechanism further validated using spatial transcriptomics. This study not only establishes physiologically relevant immuno-lung organoid models for modeling macrophage-mediated tissue damage, but also identifies a previous unrecognized role of the THBS1-(ITGA3+ITGB1) pathway in driving lung cell senescence during infectious disease.</p>\",\"PeriodicalId\":117,\"journal\":{\"name\":\"Advanced Science\",\"volume\":\" \",\"pages\":\"e03932\"},\"PeriodicalIF\":14.3000,\"publicationDate\":\"2025-07-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Science\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1002/advs.202503932\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202503932","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
A Human Immuno-Lung Organoid Model to Study Macrophage-Mediated Lung Cell Senescence Upon SARS-CoV-2 Infection.
While COVID-19 affects multiple organ systems, the human respiratory system is the primary viral target and main site for disease progression. In this study, spatial transcriptional assays (NanoString CosMx) are utilized to analyze both explant and autopsy samples from non-COVID and COVID-19 lungs, identifying the activation of proinflammatory macrophages in COVID-19 explants. It is further developed immuno-lung organoids comprising hPSC-derived alveolar and airway organoids co-cultured with macrophages to investigate the impact and underlying mechanisms of macrophage-mediated lung damage following SARS-CoV-2 infection. The findings demonstrate that proinflammatory macrophages induce lung cell senescence through the THBS1-(ITGA3+ITGB1) signaling axis, a mechanism further validated using spatial transcriptomics. This study not only establishes physiologically relevant immuno-lung organoid models for modeling macrophage-mediated tissue damage, but also identifies a previous unrecognized role of the THBS1-(ITGA3+ITGB1) pathway in driving lung cell senescence during infectious disease.
期刊介绍：
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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