Identification of factors mediating the signaling convergence of multiple receptors following cell-cell interaction
2Sackler Faculty of Medicine, Tel Aviv University, Israel
Motivation: Cell-cell crosstalk involves simultaneous interactions of multiple receptors and
ligands, followed by downstream signaling cascades working through receptors converging at
dominant transcription factors which then integrate and propagate multiple signals into a
cellular response. Single-cell RNAseq data of multiple cell subsets isolated from a defined
microenvironment provide us with a unique opportunity to learn about such interactions.
Results: We developed the FLOW framework with the intention of mapping the potential
ligand-receptor interactions between different cell subsets based on a maximum flow
computation in a network of protein-protein interactions (PPIs). FLOW further allows
characterizing the intracellular downstream signal transduction from differentially expressed
receptors towards dominant transcription factors. Importantly, we were able to identify key
transcription factors toward which the convergence of signaling of multiple receptors occurs.
These identified factors have a unique role in the integration and propagation of signaling
following cell-cell interactions.