153-Cross-tissue multicellular coordination in cancer

This paper introduces a new computational framework, CoVarNet, designed to systematically identify cross-tissue coordinated cellular modules (CMs) using single-cell transcriptomic data from both healthy human tissues and diverse cancer types. The researchers compiled extensive pan-tissue and pan-cancer single-cell atlases to define these CMs, which represent fundamental units of multicellular organization. By applying this framework, the study reveals how these CMs function in tissue homeostasis, showing dynamics related to factors like aging (e.g., in the spleen) and menopausal transitions (e.g., in the breast). Crucially, the analysis extends to cancer, demonstrating a multicellular rewiring during tumor progression characterized by the loss of healthy tissue organization and the emergence of a convergent, cancer-associated ecosystem. These findings offer new organizing principles of multicellular life, integrating spatial organization and intercellular communication in both health and disease.References: Shi Q, Chen Y, Li Y, et al. Cross-tissue multicellular coordination and its rewiring in cancer[J]. Nature, 2025: 1-10.