Temporal and spatial atlas of eosinophil specialization across tissues

Eosinophils are multifunctional granulocytes involved in immune regulation, metabolism and tissue repair; however, the extent of their heterogeneity across tissues and the principles governing their specialization are not well defined. Here, we present a single-cell transcriptomic and proteomic atlas of mouse eosinophils spanning immune, barrier and metabolic sites. By integrating transcriptional profiling, high-dimensional surface proteomics and in vivo fate mapping, we show that eosinophil identity is shaped by both tissue-derived cues and the duration of local residency. Long-lived eosinophils in the small intestine diversify into transcriptionally and phenotypically distinct subsets, whereas short-lived and intermediate-lived populations in the lungs and colon, respectively, remain comparatively uniform. We identify trajectory-associated surface markers that stratify eosinophil maturation from bone-marrow progenitors to long-term tissue-resident subsets. This atlas establishes a unified framework in which tissue-specific residency time drives eosinophil maturation and diversification, providing a molecular toolkit for resolving eosinophil states in health and disease.