Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-05-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/83584 |
| _version_ | 1797808147090374656 |
|---|---|
| author | Sandipan Dasgupta Daniella Y Dayagi Gal Haimovich Emanuel Wyler Tsviya Olender Robert H Singer Markus Landthaler Jeffrey E Gerst |
| author_facet | Sandipan Dasgupta Daniella Y Dayagi Gal Haimovich Emanuel Wyler Tsviya Olender Robert H Singer Markus Landthaler Jeffrey E Gerst |
| author_sort | Sandipan Dasgupta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:33:11Z |
| format | Article |
| id | doaj.art-92dc7283d54146dead5e2628d03760f7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T06:33:11Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-92dc7283d54146dead5e2628d03760f72023-06-09T07:38:03ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.83584Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell cultureSandipan Dasgupta0Daniella Y Dayagi1https://orcid.org/0000-0003-2310-2416Gal Haimovich2https://orcid.org/0000-0002-3360-5108Emanuel Wyler3https://orcid.org/0000-0002-9884-1806Tsviya Olender4Robert H Singer5https://orcid.org/0000-0002-6725-0093Markus Landthaler6Jeffrey E Gerst7https://orcid.org/0000-0002-8411-6881Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelBerlin Institute of Medical Systems Biology and Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, GermanyDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelDepartment of Anatomy & Structural Biology, Albert Einstein College of Medicine, New York, United StatesBerlin Institute of Medical Systems Biology and Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, GermanyDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelFull-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.https://elifesciences.org/articles/83584cell-cell RNA transfertunneling nanotubesRNA trafficking |
| spellingShingle | Sandipan Dasgupta Daniella Y Dayagi Gal Haimovich Emanuel Wyler Tsviya Olender Robert H Singer Markus Landthaler Jeffrey E Gerst Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture eLife cell-cell RNA transfer tunneling nanotubes RNA trafficking |
| title | Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture |
| title_full | Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture |
| title_fullStr | Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture |
| title_full_unstemmed | Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture |
| title_short | Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture |
| title_sort | global analysis of contact dependent human to mouse intercellular mrna and lncrna transfer in cell culture |
| topic | cell-cell RNA transfer tunneling nanotubes RNA trafficking |
| url | https://elifesciences.org/articles/83584 |
| work_keys_str_mv | AT sandipandasgupta globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT daniellaydayagi globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT galhaimovich globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT emanuelwyler globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT tsviyaolender globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT roberthsinger globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT markuslandthaler globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture AT jeffreyegerst globalanalysisofcontactdependenthumantomouseintercellularmrnaandlncrnatransferincellculture |