Abstract
<title>Abstract</title> <p>Spatial transcriptomics enables molecular characterization of tissues at cellular resolution, yet the higher-order principles governing multicellular organization remain poorly understood. Here we present CommuSpace, a computational framework that represents tissues in a communication space defined by ligand–receptormediated interactions among neighboring cellular populations. Rather than organizing cells by transcriptional identity or neighborhood composition, CommuSpace organizes them according to shared communication architectures, revealing recurrent communication ecosystems as emergent multicellular organizational states. Across neural, tumor, and injury–repair systems, CommuSpace uncovers cross-lineage cortical organization, hierarchical communication ecosystems, specialized pathological boundary states, ecosystem-associated immune remodeling, and temporally ordered tissue-repair trajectories. Together, our findings establish communication ecosystems as a previously unrecognized higher-order organizational layer of multicellular tissues that cannot be fully explained by cell identity or conventional spatial niches, providing a communication-centered framework for resolving tissue architecture.</p>