title: Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells.
abstract: Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 genomic DNA (gDNA) fragments in the EVs from human plasma. Immunofluorescence study showed direct evidence that acridine orange-stained EV DNAs could be transferred into the cells and localize to and inside the nuclear membrane. However, whether the transferred EV DNAs are functional or not is not clear. We found that EV gDNAs could be homologously or heterologously transferred from donor cells to recipient cells, and increase gDNA-coding mRNA, protein expression, and function (e.g. AT1 receptor). An endogenous promoter of the AT1 receptor, NF-κB, could be recruited to the transferred DNAs in the nucleus, and increase the transcription of AT1 receptor in the recipient cells. Moreover, the transferred EV gDNAs have pathophysiological significance. BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia, could be transferred from K562 EVs to HEK293 cells or neutrophils. Our present study shows that the gDNAs transferred from EVs to cells have physiological significance, not only to increase the gDNA-coding mRNA and protein levels, but also to influence function in recipient cells.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Eisner
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D001692:Biological Transport; D002450:Cell Communication / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D009504:Neutrophils; D022161:Transport Vesicles / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D004247:DNA
keywords: AT1 receptor; BCR/ABL hybrid gene; extracellular vesicles; genomic DNA