Molecular tools for decoding multicellular systems: from mechanisms to medicine

Abstract Cell-cell communication (CCC) is fundamental to essential biological processes including growth, differentiation, immune surveillance, and tissue homeostasis, and its dysregulation underlies various diseases such as cancer, autoimmunity, and neurodegeneration. In response to growing interest in decoding complex multicellular interactions, the 380th Shuangqing Forum entitled ‘Chemical, Biological, and Medical Frontiers in Multicellular Complex Systems’ was convened, providing a platform to discuss recent interdisciplinary breakthroughs. This review, emerging from forum discussions, highlights the latest advancements in molecular tools—such as super-resolution imaging, proximity labeling, bioorthogonal chemistry, synthetic receptors, and single-cell spatial omics—that enable unprecedented insights into spatial, molecular, and functional aspects of CCC. Emphasizing their translational potential, we discuss their profound implications for immuno-oncology, regenerative medicine, and autoimmune diseases. We further outline current challenges and opportunities, particularly advocating for a future precision medicine framework centered around targeted modulation of cell-cell interactions.