Spatiotemporal single‐cell transcriptomic profiling reveals inflammatory cell states in a mouse model of diffuse alveolar damage
Duo Su,
Zhouguang Jiao,
Sha Li,
Liya Yue,
Cuidan Li,
Mengyun Deng,
Lingfei Hu,
Lupeng Dai,
Bo Gao,
Jinglin Wang,
Hanchen Zhang,
Haihua Xiao,
Fei Chen,
Huiying Yang,
Dongsheng Zhou
Affiliations
Duo Su
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Zhouguang Jiao
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Sha Li
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Liya Yue
Laboratory of Genome Sciences & Information, Beijing Institute of Genomics Chinese Academy of Sciences and China National Center for Bioinformation Beijing China
Cuidan Li
Laboratory of Genome Sciences & Information, Beijing Institute of Genomics Chinese Academy of Sciences and China National Center for Bioinformation Beijing China
Mengyun Deng
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Lingfei Hu
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Lupeng Dai
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Bo Gao
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Jinglin Wang
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Hanchen Zhang
Beijing National Laboratory for Molecular Science, State Key Laboratory of Polymer Physical and Chemistry Institute of Chemistry, Chinese Academy of Science Beijing China
Haihua Xiao
Beijing National Laboratory for Molecular Science, State Key Laboratory of Polymer Physical and Chemistry Institute of Chemistry, Chinese Academy of Science Beijing China
Fei Chen
Laboratory of Genome Sciences & Information, Beijing Institute of Genomics Chinese Academy of Sciences and China National Center for Bioinformation Beijing China
Huiying Yang
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Dongsheng Zhou
State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China
Abstract Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single‐cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD‐induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper‐inflammatory state, and the subsequent occurrence of a CXCL1‐CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close‐knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper‐inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression.
