Deciphering cell–cell interactions and communication from gene expression

Cell–cell interactions orchestrate organismal development, homeostasis and single-cell functions. When cells do not properly interact or improperly decode molecular messages, disease ensues. Thus, the identification and quantification of intercellular signalling pathways has become a common analysis performed across diverse disciplines. The expansion of protein–protein interaction databases and recent advances in RNA sequencing technologies have enabled routine analyses of intercellular signalling from gene expression measurements of bulk and single-cell data sets. In particular, ligand–receptor pairs can be used to infer intercellular communication from the coordinated expression of their cognate genes. In this Review, we highlight discoveries enabled by analyses of cell–cell interactions from transcriptomic data and review the methods and tools used in this context. Cell–cell interactions and communication can be inferred from RNA sequencing data of, for example, ligand–receptor pairs. The authors review insights gained and the methods and tools used in studies of cell–cell interactions based on transcriptomic data.