Evidence for extensive intercellular mRNA transfer in vertebrates

It is generally believed that a cell’s mRNAs are transcribed from the cell’s own DNA. This view has, however, not been rigorously tested in multicellular organisms. We here designed an assay to quantify genome-wide intercellular mRNA transfer in vivo using chimeric zebrafish. By fusing early embryonic cells of two genetically distinct zebrafish lines (TU and TL), we created chimeric organisms in which the origin of mRNAs could be traced using divergent genomic sites between the TU and TL lines. Single-cell RNA sequencing the TL cells obtained from the chimeric organisms revealed an average of 5.8% (up to 15.7%) of the transcripts originating from TU cells, indicating widespread intercellular mRNA transfer. This transfer occurred in various cell types, exhibiting a bias toward highly expressed genes. Subsequent analyses showed that the transferred transcripts retained intact structure, and with normal biological functionality according to a Cre recombinase reporter system. Further, similar observations were made in chimeric mice, demonstrating evolutionary conservation of this phenomenon in both vertebrates. The results thus reveal unexpectedly strong intercellular mRNA transfer in vertebrates under normal physiological conditions, challenging current models of cellular autonomy in gene expression and suggesting novel biology in multicellular organisms for achieving cell-cell communication.