Abstract: Interconnected cells of the brain are the physical basis for cognition; however, electrically excitable neurons represent less than 1% of all cells in the human body. In this DP2 proposal we ask about the remaining cells. Are the vast number of non-excitable cells in the body also interconnected in similarly productive yet undiscovered cell communication networks? If so, what are their emergent functions? We propose an ambitious program that combines technologies of single cell analysis, genetic reporters, intravital microscopy, and quantitative data analysis to systematically discover cell communication networks in living tissue. We will apply these tools and techniques to the study of sterile injury and inflammation in the heart, liver, and cancer in the hopes of better understanding why some tissues fibrose and scar while others heal and regenerate.