A draft network of ligand–receptor-mediated multicellular signalling in human

Cell-to-cell communication across multiple cell types and tissues strictly governs proper
functioning of metazoans and extensively relies on interactions between secreted ligands
and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell
communication between 144 human primary cell types. We reveal that most cells express
tens to hundreds of ligands and receptors to create a highly connected signalling network
through multiple ligand–receptor paths. We also observe extensive autocrine signalling with
approximately two-thirds of partners possibly interacting on the same cell type. We find that
plasma membrane and secreted proteins have the highest cell-type specificity, they are
evolutionarily younger than intracellular proteins, and that most receptors had evolved before
their ligands. We provide an online tool to interactively query and visualize our networks and
demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that
mast cells signal to monoblastic lineages via the CSF1–CSF1R interacting pair.