Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury
Yiheng Mao,
Ying Chen,
Yuan Li,
Longda Ma,
Xi Wang,
Qi Wang,
An He,
Xi Liu,
Tianyi Dong,
Weina Gao,
Yanfen Xu,
Liang Liu,
Liang Ren,
Qian Liu,
Peng Zhou,
Ben Hu,
Yiwu Zhou,
Ruijun Tian,
Zheng-Li Shi
Affiliations
Yiheng Mao
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China; Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Ying Chen
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China; University of Chinese Academy of Sciences, Beijing, China
Yuan Li
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Longda Ma
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Xi Wang
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Qi Wang
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China; University of Chinese Academy of Sciences, Beijing, China
An He
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Xi Liu
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China; University of Chinese Academy of Sciences, Beijing, China
Tianyi Dong
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China; University of Chinese Academy of Sciences, Beijing, China
Weina Gao
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Yanfen Xu
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China
Liang Liu
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Liang Ren
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Qian Liu
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Peng Zhou
Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou 510005, China
Ben Hu
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China
Yiwu Zhou
Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding author
Ruijun Tian
Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science, Southern University of Science and Technology, Shenzhen 518055, China; Corresponding author
Zheng-Li Shi
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430030, China; Corresponding author
Summary: As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.
