1. Cell Biology

Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture

  1. Sandipan Dasgupta
  2. Daniella Y Dayagi
  3. Gal Haimovich  Is a corresponding author
  4. Emanuel Wyler
  5. Tsviya Olender
  6. Robert H Singer
  7. Markus Landthaler
  8. Jeffrey E Gerst  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Max Delbruck Center for Molecular Medicine, Switzerland
  3. Albert Einstein College of Medicine, United States
https://doi.org/10.7554/eLife.83584
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Cite this article
  1. Sandipan Dasgupta
  2. Daniella Y Dayagi
  3. Gal Haimovich
  4. Emanuel Wyler
  5. Tsviya Olender
  6. Robert H Singer
  7. Markus Landthaler
  8. Jeffrey E Gerst
(2023)
Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture
eLife 12:e83584.
https://doi.org/10.7554/eLife.83584
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Abstract

Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the 'transferome') is unknown. Here, we analyzed the transferome in an in vitro human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically, <1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.

Data availability

The processed RNA sequencing files have been deposited in the Gene Expression Omnibus (GEO) Database under the accession number GSE185002

The following data sets were generated

Article and author information

Author details

  1. Sandipan Dasgupta

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.

  2. Daniella Y Dayagi

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2310-2416

  3. Gal Haimovich

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    gal.haimovich@weizmann.ac.il
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3360-5108

  4. Emanuel Wyler

    Berlin Institute of Medical Systems Biology and Systems Biology, Max Delbruck Center for Molecular Medicine, Zurich, Switzerland
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9884-1806

  5. Tsviya Olender

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.

  6. Robert H Singer

    Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States
    Competing interests
    Robert H Singer, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6725-0093

  7. Markus Landthaler

    Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Zurich, Switzerland
    Competing interests
    No competing interests declared.

  8. Jeffrey E Gerst

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    jeffrey.gerst@weizmann.ac.il
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8411-6881

Funding

German-Israeli Foundation for Scientific Research and Development (I-1461-412.13/2018)

  • Markus Landthaler
  • Jeffrey E Gerst

US-Israel Binational Science Foundation-National Science Foundation (2015846)

  • Robert H Singer
  • Jeffrey E Gerst

Joel and Mady Dukler Fund for Cancer Research

  • Jeffrey E Gerst

Jean-Jacques Brunschwig Fund for the Molecular Genetics of Cancer

  • Jeffrey E Gerst

Moross Integrated Cancer Center

  • Jeffrey E Gerst

Kekst Family Institute for Medical Genetics

  • Jeffrey E Gerst

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

Copyright

© 2023, Dasgupta 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. Sandipan Dasgupta
  2. Daniella Y Dayagi
  3. Gal Haimovich
  4. Emanuel Wyler
  5. Tsviya Olender
  6. Robert H Singer
  7. Markus Landthaler
  8. Jeffrey E Gerst
(2023)
Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture
eLife 12:e83584.
https://doi.org/10.7554/eLife.83584

Share this article

https://doi.org/10.7554/eLife.83584

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