Abstract
Extracellular vesicles (EVs) are described as membranous vesicles that are secreted by various cell types. EVs can be categorised as exosomes, ectosomes, apoptotic bodies, large oncosomes and migrasomes. EVs are heterogeneous in nature according to their origin, mode of release, size, and biochemical contents. Herein, we discuss a recently discovered subpopulation of EVs called ‘exomeres’. Unlike the other subtypes of EVs, exomeres are defined as non-membranous nanovesicles with a size ≤50 nm. They can be isolated using asymmetric-flow field-flow fractionation as well as ultracentrifugation. The cargo of exomeres are beginning to be unravelled and are highlighted to be enriched with proteins implicated in regulating metabolic pathways. Consistent with other types of EVs, exomeres also contain nucleic acids and lipids which can be delivered to recipient cells. These discoveries highlight the complex heterogeneity of EVs and thereby necessitates further attention to understand the nature of each subpopulation more exclusively. Overall, this chapter describes the current knowledge on exomeres.
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References
Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci USA 106(10):3794–3799
Anand S, Samuel M, Kumar S, Mathivanan S (2019) Ticket to a bubble ride: cargo sorting into exosomes and extracellular vesicles. Biochim Biophys Acta Proteins Proteom 1867(12):140203
Boukouris S, Mathivanan S (2015) Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteomics Clin Appl 9(3–4):358–367
Chuo ST-Y, Chien JC-Y, Lai CP-K (2018) Imaging extracellular vesicles: current and emerging methods. J Biomed Sci 25(1):91
Fonseka P, Liem M, Ozcitti C, Adda CG, Ang CS, Mathivanan S (2019) Exosomes from N-Myc amplified neuroblastoma cells induce migration and confer chemoresistance to non-N-Myc amplified cells: implications of intra-tumor heterogeneity. J Extracell Vesicles 8(1):1597614
Giddings JC, Yang FJ, Myers MN (1976) Flow-field-flow fractionation: a versatile new separation method. Science 193(4259):1244–1245
Granger J, Dodds J, Leclerc D, Midoux N (1986) Flow and diffusion of particles in a channel with one porous wall: polarization chromatography. Chem Eng Sci 41(12):3119–3128
Hoshino A, Costa-Silva B, Shen T-L, Rodrigues G, Hashimoto A, Mark MT, Molina H, Kohsaka S, Di Giannatale A, Ceder S (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527(7578):329–335
Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Mark MT, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Vatter FAP, Hashimoto A, Davies AE, Freitas D, Kenific CM, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Alečković M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, García-Santos G, Posner Z, Balachandran VP, Khakoo Y, Raju GP, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Malladi M, Petriccione M, De Braganca KC, Donzelli M, Fischer C, Vitolano S, Wright GP, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MHA, Lacayo NJ, Vincent TC, Weiser MR, Brady MS, Meyers PA, Wexler LH, Ambati SR, Chou AJ, Slotkin EK, Modak S, Roberts SS, Basu EM, Diolaiti D, Krantz BA, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Blavier L, De Clerck YA, La Barge M, Bissell MJ, Caffrey TC, Grandgenett PM, Hollingsworth MA, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O’Reilly EM, Kelsen D, Trippett TM, Jones DR, Matei IR, Jarnagin WR, Lyden D (2020) Extracellular vesicle and particle biomarkers define multiple human cancers. Cell 182(4):1044–1061.e1018
Huang G, Lin G, Zhu Y, Duan W, Jin D (2020) Emerging technologies for profiling extracellular vesicle heterogeneity. Lab Chip 20(14):2423–2437
Kalra H, Drummen GP, Mathivanan S (2016) Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci 17(2):170
Kalra H, Gangoda L, Fonseka P, Chitti SV, Liem M, Keerthikumar S, Samuel M, Boukouris S, Al Saffar H, Collins C, Adda CG, Ang CS, Mathivanan S (2019) Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells. J Extracell Vesicles 8(1):1690217
Keerthikumar S, Gangoda L, Liem M, Fonseka P, Atukorala I, Ozcitti C, Mechler A, Adda CG, Ang CS, Mathivanan S (2015) Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes. Oncotarget 6(17):15375–15396
Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K, Samuel M, Pathan M, Jois M, Chilamkurti N, Gangoda L, Mathivanan S (2016) ExoCarta: a web-based compendium of exosomal cargo. J Mol Biol 428(4):688–692
Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Thery C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA 113(8):E968–E977
Lässer C, Eldh M, Lötvall J (2012) Isolation and characterization of RNA-containing exosomes. J Vis Exp 59:e3037
Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: Extracellular organelles important in intercellular communication. J Proteome 73(10):1907–1920
Merchant ML, Powell DW, Wilkey DW, Cummins TD, Deegens JK, Rood IM, McAfee KJ, Fleischer C, Klein E, Klein JB (2010) Microfiltration isolation of human urinary exosomes for characterization by MS. Proteomics Clin Appl 4(1):84–96
Multia E, Liangsupree T, Jussila M, Ruiz-Jimenez J, Kemell M, Riekkola ML (2020) Automated on-line isolation and fractionation system for nanosized biomacromolecules from human plasma. Anal Chem 92:13058–13065
Pathan M, Fonseka P, Chitti SV, Kang T, Sanwlani R, Van Deun J, Hendrix A, Mathivanan S (2019) Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Res 47(D1):D516–D519
Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891
Sanwlani R, Fonseka P, Chitti SV, Mathivanan S (2020) Milk-derived extracellular vesicles in inter-organism, cross-species communication and drug delivery. Proteomes 8(2):11
Tai YL, Chen KC, Hsieh JT, Shen TL (2018) Exosomes in cancer development and clinical applications. Cancer Sci 109(8):2364–2374
Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56(2):293–304
Théry C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol 30(1):3.22.21–23.22.29
Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, Ayre DC, Bach JM, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer NN, Baxter AA, Bebawy M, Beckham C, Zavec AB, Benmoussa A, Berardi AC, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borras FE, Bosch S, Boulanger CM, Breakefield X, Breglio AM, Brennan MA, Brigstock DR, Brisson A, Broekman ML, Bromberg JF, Bryl-Gorecka P, Buch S, Buck AH, Burger D, Busatto S, Buschmann D, Bussolati B, Buzas EI, Byrd JB, Camussi G, Carter DR, Caruso S, Chamley LW, Chang YT, Chen C, Chen S, Cheng L, Chin AR, Clayton A, Clerici SP, Cocks A, Cocucci E, Coffey RJ, Cordeiro-da-Silva A, Couch Y, Coumans FA, Coyle B, Crescitelli R, Criado MF, D'Souza-Schorey C, Das S, Chaudhuri AD, de Candia P, De Santana EF, De Wever O, Del Portillo HA, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich LC, Dolo V, Rubio APD, Dominici M, Dourado MR, Driedonks TA, Duarte FV, Duncan HM, Eichenberger RM, Ekstrom K, El Andaloussi S, Elie-Caille C, Erdbrugger U, Falcon-Perez JM, Fatima F, Fish JE, Flores-Bellver M, Forsonits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gamez-Valero A, Gardiner C, Gartner K, Gaudin R, Gho YS, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan DC, Gorgens A, Gorski SM, Greening DW, Gross JC, Gualerzi A, Gupta GN, Gustafson D, Handberg A, Haraszti RA, Harrison P, Hegyesi H, Hendrix A, Hill AF, Hochberg FH, Hoffmann KF, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim AG, Ikezu T, Inal JM, Isin M, Ivanova A, Jackson HK, Jacobsen S, Jay SM, Jayachandran M, Jenster G, Jiang L, Johnson SM, Jones JC, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano SI, Kaur S, Kawamura Y, Keller ET, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim KP, Kislinger T, Klingeborn M, Klinke DJ 2nd, Kornek M, Kosanovic MM, Kovacs AF, Kramer-Albers EM, Krasemann S, Krause M, Kurochkin IV, Kusuma GD, Kuypers S, Laitinen S, Langevin SM, Languino LR, Lannigan J, Lasser C, Laurent LC, Lavieu G, Lazaro-Ibanez E, Le Lay S, Lee MS, Lee YXF, Lemos DS, Lenassi M, Leszczynska A, Li IT, Liao K, Libregts SF, Ligeti E, Lim R, Lim SK, Line A, Linnemannstons K, Llorente A, Lombard CA, Lorenowicz MJ, Lorincz AM, Lotvall J, Lovett J, Lowry MC, Loyer X, Lu Q, Lukomska B, Lunavat TR, Maas SL, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova ES, Martin-Jaular L, Martinez MC, Martins VR, Mathieu M, Mathivanan S, Maugeri M, McGinnis LK, McVey MJ, Meckes DG Jr, Meehan KL, Mertens I, Minciacchi VR, Moller A, Jorgensen MM, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth DC, Myburgh KH, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan JP, Nolte-t’ Hoen EN, Hooten NN, O’Driscoll L, O’Grady T, O’Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz LA, Osteikoetxea X, Ostergaard O, Ostrowski M, Park J, Pegtel DM, Peinado H, Perut F, Pfaffl MW, Phinney DG, Pieters BC, Pink RC, Pisetsky DS, von Strandmann EP, Polakovicova I, Poon IK, Powell BH, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai RL, Raimondo S, Rak J, Ramirez MI, Raposo G, Rayyan MS, Regev-Rudzki N, Ricklefs FL, Robbins PD, Roberts DD, Rodrigues SC, Rohde E, Rome S, Rouschop KM, Rughetti A, Russell AE, Saa P, Sahoo S, Salas-Huenuleo E, Sanchez C, Saugstad JA, Saul MJ, Schiffelers RM, Schneider R, Schoyen TH, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke GV, Shetty AK, Shiba K, Siljander PR, Silva AM, Skowronek A, Snyder OL 2nd, Soares RP, Sodar BW, Soekmadji C, Sotillo J, Stahl PD, Stoorvogel W, Stott SL, Strasser EF, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh WS, Tomasini R, Torrecilhas AC, Tosar JP, Toxavidis V, Urbanelli L, Vader P, van Balkom BW, van der Grein SG, Van Deun J, van Herwijnen MJ, Van Keuren-Jensen K, van Niel G, van Royen ME, van Wijnen AJ, Vasconcelos MH, Vechetti IJ Jr, Veit TD, Vella LJ, Velot E, Verweij FJ, Vestad B, Vinas JL, Visnovitz T, Vukman KV, Wahlgren J, Watson DC, Wauben MH, Weaver A, Webber JP, Weber V, Wehman AM, Weiss DJ, Welsh JA, Wendt S, Wheelock AM, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yanez-Mo M, Yin H, Yuana Y, Zappulli V, Zarubova J, Zekas V, Zhang JY, Zhao Z, Zheng L, Zheutlin AR, Zickler AM, Zimmermann P, Zivkovic AM, Zocco D, Zuba-Surma EK (2018) 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. J Extracell Vesicles 7(1):1535750
Urbanelli L, Buratta S, Sagini K, Ferrara G, Lanni M, Emiliani C (2015) Exosome-based strategies for diagnosis and therapy. Recent Pat CNS Drug Discov 10(1):10–27
Willms E, Cabañas C, Mäger I, Wood MJA, Vader P (2018) Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression. Front Immunol 9:738–738
Witwer KW, Soekmadji C, Hill AF, Wauben MH, Buzas EI, Di Vizio D, Falcon-Perez JM, Gardiner C, Hochberg F, Kurochkin IV, Lotvall J, Mathivanan S, Nieuwland R, Sahoo S, Tahara H, Torrecilhas AC, Weaver AM, Yin H, Zheng L, Gho YS, Quesenberry P, Thery C (2017) Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility. J Extracell Vesicles 6(1):1396823
Zhang H, Lyden D (2019) Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization. Nat Protoc 14(4):1027–1053
Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific CM, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferreira JA, Osorio H, Silva AM, Massey A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D (2018) Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 20(3):332–343
Zhang Q, Higginbotham JN, Jeppesen DK, Yang YP, Li W, McKinley ET, Graves-Deal R, Ping J, Britain CM, Dorsett KA, Hartman CL, Ford DA, Allen RM, Vickers KC, Liu Q, Franklin JL, Bellis SL, Coffey RJ (2019) Transfer of functional cargo in exomeres. Cell Rep 27(3):940–954.e946
Zhao K, Bleackley M, Chisanga D, Gangoda L, Fonseka P, Liem M, Kalra H, Al Saffar H, Keerthikumar S, Ang CS, Adda CG, Jiang L, Yap K, Poon IK, Lock P, Bulone V, Anderson M, Mathivanan S (2019) Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling. Commun Biol 2:305
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Anand, S., Samuel, M., Mathivanan, S. (2021). Exomeres: A New Member of Extracellular Vesicles Family. In: Mathivanan, S., Fonseka, P., Nedeva, C., Atukorala, I. (eds) New Frontiers: Extracellular Vesicles. Subcellular Biochemistry, vol 97. Springer, Cham. https://doi.org/10.1007/978-3-030-67171-6_5
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