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      DNA in extracellular vesicles: biological and clinical aspects

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          Abstract

          The presence of DNA in EVs, including exosomes and microvesicles, remains contentious as this field of study is still evolving. This review explores what is known about the biogenesis of EV‐DNA and the possible biological roles of DNA packaging into EVs. Moreover, we also discuss the potential clinical applications of EV‐DNA and how those compare to cell‐free DNA.

          Abstract

          The study of extracellular vesicles (EVs), especially in the liquid biopsy field, has rapidly evolved in recent years. However, most EV studies have focused on RNA or protein content and DNA in EVs (EV‐DNA) has largely been unnoticed. In this review, we compile current evidence regarding EV‐DNA and provide an extensive discussion on EV‐DNA biology. We look into EV‐DNA biogenesis and mechanisms of DNA loading into EVs, as well as describe the particularly significant function of DNA‐carrying EVs in the maintenance of cellular homeostasis, intracellular communication, and immune response modulation. We also examine the current role of EV‐DNA in the clinical setting, specifically in cancer, infections, pregnancy, and prenatal diagnosis.

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)
          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            The biology, function, and biomedical applications of exosomes

            Raghu Kalluri, Valerie LeBleu (2020)
            The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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              Biological properties of extracellular vesicles and their physiological functions

              María Yañez-Mó, Pia Siljander, Zoraida Andreu … (2015)
              In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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                Author and article information

                Contributors
                Bruno Costa‐Silva:
                ORCID: https://orcid.org/0000-0002-5932-6211
                bruno.costa-silva@research.fchampalimaud.org
                Journal
                Journal ID (nlm-ta): Mol Oncol
                Journal ID (iso-abbrev): Mol Oncol
                Journal ID (doi): 10.1002/(ISSN)1878-0261
                Journal ID (publisher-id): MOL2
                Title: Molecular Oncology
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1574-7891
                ISSN (Electronic): 1878-0261
                Publication date (Electronic): 19 August 2020
                Publication date (Print): June 2021
                Volume: 15
                Issue: 6 ( doiID: 10.1002/mol2.v15.6 )
                Pages: 1701-1714
                Affiliations
                [ 1 ] Champalimaud Research Champalimaud Centre for the Unknown Lisbon Portugal
                Author notes
                [*] [* ] Correspondence

                B. Costa‐Silva, Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon 1400‐038, Portugal

                Tel: +351 210 480 134

                E‐mail: bruno.costa-silva@ 123456research.fchampalimaud.org

                Author information
                https://orcid.org/0000-0002-5932-6211
                Article
                Publisher ID: MOL212777
                DOI: 10.1002/1878-0261.12777
                PMC ID: 8169445
                PubMed ID: 32767659
                SO-VID: d31efe7b-6251-4b9a-9de1-6e4a2f8e3a79
                Copyright © © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 28 July 2020
                Date received : 01 June 2020
                Date accepted : 03 August 2020
                Page count
                Figures: 2, Tables: 1, Pages: 14, Words: 9738
                Funding
                Funded by: H2020‐MSCA‐ITN‐2017
                Award ID: 765492
                Funded by: EMBO Installation Grant
                Award ID: 3921
                Funded by: Champalimaud Foundation
                Funded by: “La Caixa” Foundation
                Award ID: LCF/PR/HR19/52160014
                Funded by: Breast Cancer Now’s Catalyst Programme, which is supported by funding from Pfizer
                Award ID: 2017NovPCC1058
                Categories
                Subject: Review
                Subject: Reviews
                Custom metadata
                source-schema-version-number 2.0
                cover-date June 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:01.06.2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer,cell‐free dna,ev‐dna,extracellular vesicles,infection,liquid biopsies
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer, cell‐free dna, ev‐dna, extracellular vesicles, infection, liquid biopsies

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