Genetic dissection of intercellular interactions in vivo by membrane-permeable protein

Unraveling cell-cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell-cell interactions and communications in vivo.

Automated summary

Understanding cell-cell interactions is crucial for understanding biological processes. In this study, we developed a labeling strategy called Cre-induced intercellular labeling protein (CILP) to label neighboring cells in mammals. By using CILP, we successfully labeled endothelial cells in adult mice and revealed their gene signatures.