Spatiotemporal single‐cell transcriptomic profiling reveals inflammatory cell states in a mouse model of diffuse alveolar damage

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about distinct roles tissue structural cells modulating recruitment neutrophils to areas. Here, by combining single-cell and spatial transcriptomics, using quantitative assays, we systematically analyze inflammatory cell states a mouse model DAD-induced after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch hyper-inflammatory state, subsequent occurrence CXCL1-CXCR2 chemokine axis between activated (AFib) as signal sender receiver further neutrophil recruitment. also identify an anatomically localized inflamed niche (characterized close-knit intercellular contact recruited AFib) peribronchial regions facilitate pulmonary outbreak. Our findings intricate interplay provide overarching profile dynamically changing microenvironments during DAD progression.