biostudies-literatureTang RTobacco-Related Disease Research ProgramStanford UniversityStanford University School of MedicineNational Cancer InstituteNational Institutes of HealthNational Science Foundatione61080https://www.ebi.ac.uk/biostudies/studies/S-EPMC7682987biostudies-literatureUnknown9Cell-cell interactions influence all aspects of development, homeostasis, and disease. In cancer, interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis. Thus, the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of the cancer microenvironment. Here, we describe GFP-based Touching Nexus (G-baToN) which relies upon nanobody-directed fluorescent protein transfer to enable sensitive and specific labeling of cells after cell-cell interactions. G-baToN is a generalizable system that enables physical contact-based labeling between various human and mouse cell types, including endothelial cell-pericyte, neuron-astrocyte, and diverse cancer-stromal cell pairs. A suite of orthogonal baToN tools enableeLifeA versatile system to record cell-cell interactions.PMC7682987R01-CA230919R01-CA17533627FT-0044R01-CA207133K25-CA201545Dean’s Postdoctoral FellowshipAnne T. and Robert M. Bass FellowshipCA196029Graduate Research Fellowship ProgramWinslow MMChen LCGitler ADLyu ZMurray CWTsai MKTang REngleman ELinde ILLee WKramer NJCai HfalseA versatile system to record cell-cell interactions.Cell-cell interactions influence all aspects of development, homeostasis, and disease. In cancer, interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis. Thus, the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of the cancer microenvironment. Here, we describe GFP-based Touching Nexus (G-baToN) which relies upon nanobody-directed fluorescent protein transfer to enable sensitive and specific labeling of cells after cell-cell interactions. G-baToN is a generalizable system that enables physical contact-based labeling between various human and mouse cell types, including endothelial cell-pericyte, neuron-astrocyte, and diverse cancer-stromal cell pairs. A suite of orthogonal baToN tools enable2020-01-01T00:00:00Z2020 Oct2025-04-04T10:11:15.78Z2021-02-20T00:27:58ZS-EPMC76829873302590610.7554/eLife.61080