Elsevier

Experimental Cell Research

Volume 349, Issue 1, 15 November 2016, Pages 179-183
Experimental Cell Research

Review Article
Functional transferred DNA within extracellular vesicles

https://doi.org/10.1016/j.yexcr.2016.10.012Get rights and content

Highlights

  • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases.

  • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases.

  • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.

Abstract

Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmic macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs.

Section snippets

Characterization of EVs

Extracellular vesicles (EVs) are small membrane vesicles, such as exosomes and shedding vesicles, which can be released from almost all cell types, induced by various stimuli or occur spontaneously [1], [2]. Exosomes are small EVs ranging in size between 50 nm and 100 nm in diameter, with a density of 1.10–1.21 g/ml [3]. They are released upon exocytosis of multivesicular bodies (MVBs), triggered by key molecules including sphingolipid ceramide and ALG-2 interacting protein X (ALIX) [1], [4], [5] (

Transferred DNA within EVs

EVs may vary in their formation, size, abundance, and composition, but they often contain abundant transmembrane and cytosolic proteins, mRNAs, miRNAs, and DNAs [4], [12], [13], [14] (Fig. 1). EVs allow the horizontal transfer of borne molecules from one cell to another, which are shed from almost all cell types under both physiological and pathological conditions [1], [4]. Importantly, the transferred components in EVs are functional and can regulate the biological functions of the recipient

Characteristics of DNA in EVs

To reduce the external DNA contamination, isolated EVs are extensively treated with DNase before DNA extraction to remove the DNA exterior to the EVs. External DNase digestion should now be part of the standard procedure when isolating EVs for nucleic acid analysis [26]. Recent studies have shown that both mitochondrial DNA (mtDNA) and chromosomal DNA are found in EVs [27], [28], [29], [30]. Guescini et al. provide evidence that glioblastoma, astrocyte, and myoblast cells release EVs, which

Biological functions of DNA in EVs

The biological functions of EVs include secretion, immunomodulation, coagulation, and intercellular communication, and cell-to-cell communication is focused in many studies. Of the components within EVs, DNA occurs prominently in EVs during cell death or activation. The presence of DNA in plasma EVs from apoptotic cells is accessible to anti-DNA antibody binding, displaying important immunological effects [39]. Further study has shown that the existence of DNAs in EVs that could be transferred

Cardiovascular diseases

The transfer of DNA in EVs from cardiomyocytes can affect the expressions of the identified genes in recipient fibroblasts [27]. This finding indicates that this horizontal DNA transfer may be related to cardiomyopathies. Consistent with the study above, we have found an endogenous promoter of the AT1R, NF-κβ, can be recruited to the transferred AT1R gene in the nucleus, and increase the transcription of AT1R in the recipient VSMCs [22]. The result shows that the transferred AT1R gene by EVs

Future perspectives

The specific interaction of EVs with recipient cells is followed by either direct fusion or programmed endocytosis. The consequences of the interaction are involved in signal transduction and horizontal transfer among cells. Especially, EVs are now recognized to have important roles in the transfer of gene products including RNA and protein, or even DNA. Horizontal gene transfer by EVs is up to recently considered impossible, for the view that the intercellular DNA transfer has often been

Author contribution

This review was drafted by Jin Cai, supervised by Chunyu Zeng, and critical revised by Gengze Wu, Pedro A. Jose, and Chunyu Zeng.

Disclosures

The authors declare no conflict of interest.

Acknowledgments

These studies were supported in part by grants from National Basic Research Program of China (2013CB531104), and National Natural Science Foundation of China (31430043 and 81400332).

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