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

Authors :
Dasgupta S
Dayagi DY
Haimovich G
Wyler E
Olender T
Singer RH
Landthaler M
Gerst JE
Source :
ELife [Elife] 2023 May 30; Vol. 12. Date of Electronic Publication: 2023 May 30.
Publication Year :
2023

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.<br />Competing Interests: SD, DD, GH, EW, TO, ML, JG No competing interests declared, RS Reviewing editor, eLife<br /> (© 2023, Dasgupta et al.)

Details

Language :
English
ISSN :
2050-084X
Volume :
12
Database :
MEDLINE
Journal :
ELife
Publication Type :
Academic Journal
Accession number :
37249209
Full Text :
https://doi.org/10.7554/eLife.83584