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

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Item Type:Article
Title:Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture
Creators Name:Dasgupta, S. and Dayagi, D.Y. and Haimovich, G. and Wyler, E. and Olender, T. and Singer, R.H. and Landthaler, M. and Gerst, J.E.
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 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.
Keywords:Cell Communication, Cell Culture Techniques, Fibroblasts, Long Noncoding RNA, Mammals, Messenger RNA, Nanotubes, Animals, Mice
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications
Volume:12
Page Range:e83584
Date:30 May 2023
Official Publication:https://doi.org/10.7554/eLife.83584
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/21438/Preprint version

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