This review summarizes emerging spatially resolved multi-omics approaches revealing organized cell–cell interactions in skeletal muscle and brain inflammation. These tools uncover radiating molecular programs and niche-specific immunopathology that shape cellular reactivity and vulnerability.

ABSTRACT

Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber-type-specific vulnerability, regenerative trajectories, and immune–stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single-cell gene expression enables inference of cell–cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue-resident immune programs, and guide mechanism-based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.