{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:58:49Z","timestamp":1790150329091,"version":"4.0.1"},"reference-count":33,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA175336"],"award-info":[{"award-number":["R01-CA175336"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA207133"],"award-info":[{"award-number":["R01-CA207133"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA230919"],"award-info":[{"award-number":["R01-CA230919"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005188","name":"Tobacco-Related Disease Research Program","doi-asserted-by":"publisher","award":["27FT-0044"],"award-info":[{"award-number":["27FT-0044"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Graduate Research Fellowship Program"],"award-info":[{"award-number":["Graduate Research Fellowship Program"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005492","name":"Stanford University","doi-asserted-by":"publisher","award":["Anne T. and Robert M. Bass Fellowship"],"award-info":[{"award-number":["Anne T. and Robert M. Bass Fellowship"]}],"id":[{"id":"10.13039\/100005492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA196029"],"award-info":[{"award-number":["CA196029"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K25-CA201545"],"award-info":[{"award-number":["K25-CA201545"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006521","name":"Stanford University School of Medicine","doi-asserted-by":"publisher","award":["Dean\u2019s Postdoctoral Fellowship"],"award-info":[{"award-number":["Dean\u2019s Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/100006521","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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 enables reciprocal cell-cell labeling, interaction-dependent cargo transfer, and the identification of higher order cell-cell interactions across a wide range of cell types. The ability to track physically interacting cells with these simple and sensitive systems will greatly accelerate our understanding of the outputs of cell-cell interactions in cancer as well as across many biological processes.<\/jats:p>","DOI":"10.7554\/elife.61080","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T08:01:13Z","timestamp":1602057673000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.61080","source":"Crossref","is-referenced-by-count":51,"title":["A versatile system to record cell-cell interactions"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6950-9580","authenticated-orcid":true,"given":"Rui","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-2053","authenticated-orcid":true,"given":"Christopher W","family":"Murray","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian L","family":"Linde","sequence":"additional","affiliation":[{"name":"Immunology Program, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-8343","authenticated-orcid":true,"given":"Nicholas J","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"},{"name":"Neuroscience Program, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglin","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min K","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4950-0757","authenticated-orcid":true,"given":"Leo C","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-1526","authenticated-orcid":true,"given":"Aaron D","family":"Gitler","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-9279","authenticated-orcid":true,"given":"Edgar","family":"Engleman","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Stanford University School of Medicine, Stanford, United States"},{"name":"Immunology Program, Stanford University School of Medicine, Stanford, United States"},{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonjae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-9573","authenticated-orcid":true,"given":"Monte M","family":"Winslow","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United States"},{"name":"Cancer Biology Program, Stanford University School of Medicine, Stanford, United States"},{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,10,7]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/676731","article-title":"Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins","volume":"2012","author":"Bendas","year":"2012","journal-title":"International Journal of Cell Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/s41592-018-0009-z","article-title":"Mapping the physical network of cellular interactions","volume":"15","author":"Boisset","year":"2018","journal-title":"Nature Methods"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.coi.2012.12.003","article-title":"T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment","volume":"25","author":"Crespo","year":"2013","journal-title":"Current Opinion in Immunology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1093\/cvr\/cvu054","article-title":"Cell-cell interaction in the heart via wnt\/\u03b2-catenin pathway after cardiac injury","volume":"102","author":"Deb","year":"2014","journal-title":"Cardiovascular Research"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.3892\/ijo.2014.2385","article-title":"Paracrine effects of stem cells in wound healing and Cancer progression (Review)","volume":"44","author":"Dittmer","year":"2014","journal-title":"International Journal of Oncology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1146\/annurev-cellbio-100814-125330","article-title":"Signaling and polarized communication across the T cell immunological synapse","volume":"32","author":"Dustin","year":"2016","journal-title":"Annual Review of Cell and Developmental Biology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nmeth.3170","article-title":"A robust pipeline for rapid production of versatile nanobody repertoires","volume":"11","author":"Fridy","year":"2014","journal-title":"Nature Methods"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/s41587-020-0442-2","article-title":"Dissecting cellular crosstalk by sequencing physically interacting cells","volume":"38","author":"Giladi","year":"2020","journal-title":"Nature Biotechnology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/nbt.4231","article-title":"Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells","volume":"36","author":"Halpern","year":"2018","journal-title":"Nature Biotechnology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1126\/science.aaa6204","article-title":"T cell exclusion, immune privilege, and the tumor microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s12307-009-0032-9","article-title":"Cancer-stromal cell interaction and tumor angiogenesis in gastric Cancer","volume":"3","author":"Kitadai","year":"2010","journal-title":"Cancer Microenvironment"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/path.4824","article-title":"CAFs and TAMs: maestros of the tumour microenvironment","volume":"241","author":"Komohara","year":"2017","journal-title":"The Journal of Pathology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1146\/annurev-bioeng-090215-112735","article-title":"Innovative tools and technology for analysis of single cells and Cell-Cell interaction","volume":"18","author":"Konry","year":"2016","journal-title":"Annual Review of Biomedical Engineering"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.canlet.2016.12.035","article-title":"Pancreatic Cancer: stroma and its current and emerging targeted therapies","volume":"391","author":"Kota","year":"2017","journal-title":"Cancer Letters"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1016\/j.cell.2017.10.048","article-title":"Epsin-Dependent ligand endocytosis activates notch by force","volume":"171","author":"Langridge","year":"2017","journal-title":"Cell"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41592-018-0305-7","article-title":"T cell antigen discovery via trogocytosis","volume":"16","author":"Li","year":"2019","journal-title":"Nature Methods"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/bit.24605","article-title":"Stable, high-affinity streptavidin monomer for protein labeling and monovalent biotin detection","volume":"110","author":"Lim","year":"2013","journal-title":"Biotechnology and Bioengineering"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1021\/cb800025k","article-title":"HaloTag: a novel protein labeling technology for cell imaging and protein analysis","volume":"3","author":"Los","year":"2008","journal-title":"ACS Chemical Biology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.ccell.2018.07.009","article-title":"Notch Signaling in the Tumor Microenvironment","volume":"34","author":"Meurette","year":"2018","journal-title":"Cancer Cell"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.cell.2016.01.012","article-title":"Engineering customized cell sensing and response behaviors using synthetic notch receptors","volume":"164","author":"Morsut","year":"2016","journal-title":"Cell"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nri.2017.49","article-title":"Chemokines in the Cancer microenvironment and their relevance in Cancer immunotherapy","volume":"17","author":"Nagarsheth","year":"2017","journal-title":"Nature Reviews Immunology"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i9.2678","article-title":"Key players in pancreatic cancer-stroma interaction: cancer-associated fibroblasts, endothelial and inflammatory cells","volume":"22","author":"Nielsen","year":"2016","journal-title":"World Journal of Gastroenterology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41586-019-1487-6","article-title":"Metastatic-niche labelling reveals parenchymal cells with stem features","volume":"572","author":"Ombrato","year":"2019","journal-title":"Nature"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.4161\/cc.5.15.3112","article-title":"Stromal fibroblasts in Cancer: a novel tumor-promoting cell type","volume":"5","author":"Orimo","year":"2006","journal-title":"Cell Cycle"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw0902","article-title":"CTLA-4-mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells","volume":"4","author":"Ovcinnikovs","year":"2019","journal-title":"Science Immunology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/nature25442","article-title":"Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling","volume":"553","author":"Pasqual","year":"2018","journal-title":"Nature"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1158\/0008-5472.CAN-12-0122","article-title":"Tumor microenvironment complexity: emerging roles in Cancer therapy: figure 1","volume":"72","author":"Swartz","year":"2012","journal-title":"Cancer Research"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cell.2014.09.039","article-title":"A protein-tagging system for signal amplification in gene expression and fluorescence imaging","volume":"159","author":"Tanenbaum","year":"2014","journal-title":"Cell"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1146\/annurev-chembioeng-060713-035958","article-title":"A new toolbox for assessing single cells","volume":"5","author":"Tsioris","year":"2014","journal-title":"Annual Review of Chemical and Biomolecular Engineering"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41586-019-1563-y","article-title":"Electrical and synaptic integration of glioma into neural circuits","volume":"573","author":"Venkatesh","year":"2019","journal-title":"Nature"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.tins.2011.12.003","article-title":"The Cis side of juxtacrine signaling: a new role in the development of the nervous system","volume":"35","author":"Yaron","year":"2012","journal-title":"Trends in Neurosciences"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s41586-019-1576-6","article-title":"Synaptic proximity enables NMDAR signalling to promote brain metastasis","volume":"573","author":"Zeng","year":"2019","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.tcb.2019.02.006","article-title":"Multidimensional Single-Cell analyses in organ development and maintenance","volume":"29","author":"Zhang","year":"2019","journal-title":"Trends in Cell Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/61080\/elife-61080-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/61080\/elife-61080-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/61080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:16:53Z","timestamp":1697059013000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/61080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,7]]},"references-count":33,"alternative-id":["10.7554\/eLife.61080"],"URL":"https:\/\/doi.org\/10.7554\/elife.61080","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.61080.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.61080.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,7]]},"article-number":"e61080"}}