Abstract

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 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Rui Tang

    Genetics, Stanford University School of Medicine, Stanford, United States
    For correspondence
    tangrui@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6950-9580
  2. Christopher W Murray

    Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ian L Linde

    Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicholas J Kramer

    Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4557-8343
  5. Zhonglin Lyu

    Neurosurgery, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Min K Tsai

    Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Leo C Chen

    Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4950-0757
  8. Hongchen Cai

    Department of Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Aaron D Gitler

    Department of Genetics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8603-1526
  10. Edgar Engleman

    Pathology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2096-9279
  11. Wonjae Lee

    Neurosurgery, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Monte M Winslow

    Genetics, Stanford University School of Medicine, Stanford, United States
    For correspondence
    mwinslow@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5730-9573

Funding

National Cancer Institute (CA175336)

  • Monte M Winslow

National Cancer Institute (CA207133)

  • Monte M Winslow

National Cancer Institute (CA230919)

  • Monte M Winslow

Tobacco-Related Disease Research Program (27FT-0044)

  • Rui Tang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matthew G Vander Heiden, Massachusetts Institute of Technology, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee ( the Administrative Panel on Laboratory Animal Care (APLAC)) protocols (26696) of Stanford University. The protocol was approved by the Committee on the Ethics of Animal Experiments of Stanford University (Permit Number: A3213-01). Every effort was made to minimize suffering.

Version history

  1. Received: July 15, 2020
  2. Accepted: October 6, 2020
  3. Accepted Manuscript published: October 7, 2020 (version 1)
  4. Version of Record published: November 23, 2020 (version 2)

Copyright

© 2020, Tang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Rui Tang
  2. Christopher W Murray
  3. Ian L Linde
  4. Nicholas J Kramer
  5. Zhonglin Lyu
  6. Min K Tsai
  7. Leo C Chen
  8. Hongchen Cai
  9. Aaron D Gitler
  10. Edgar Engleman
  11. Wonjae Lee
  12. Monte M Winslow
(2020)
A versatile system to record cell-cell interactions
eLife 9:e61080.
https://doi.org/10.7554/eLife.61080

Share this article

https://doi.org/10.7554/eLife.61080

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