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.
Clinically important diseases ranging from heart attack and stroke to lung, liver, and kidney failure begin with tissue injury and inflammation. It remains unknown why some tissues heal and others scar, but attempts to answer this riddle through analysis of single cell types has come up short. In this grant, we will image dynamic fluorescent reporters in living mice during tissue injury and healing to uncover the molecular conversations that transpire between its diverse cell types; doing so will identify new cell communication mechanisms that can be harnessed to promote tissue repair and regeneration.