Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture
- Weizmann Institute of Science, Israel
- Max Delbruck Center for Molecular Medicine, Switzerland
- Albert Einstein College of Medicine, United States
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
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NGS Analysis of human mRNAs in mouse cells following a 12-hr 2D-cocultureNCBI Gene Expression Omnibus, GSE185002.
Article and author information
Author details
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.
Reviewing Editor
- Gene W Yeo, University of California, San Diego, United States
Version history
- Preprint posted: November 28, 2021 (view preprint)
- Received: September 20, 2022
- Accepted: May 29, 2023
- Accepted Manuscript published: May 30, 2023 (version 1)
- Version of Record published: June 9, 2023 (version 2)
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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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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