Composition of Caenorhabditis elegans extracellular vesicles suggests roles in metabolism, immunity, and aging

Abstract

Cells from bacteria to human release vesicles into their extracellular environment. These extracellular vesicles (EVs) contain multiple classes of molecules, including nucleic acids, proteins, and lipids. The isolation and analysis of EV cargos from mammalian cell culture and liquid biopsy samples has become a powerful approach for uncovering the messages that are packaged into these organelles. However, this approach has not been tenable in invertebrate model systems due to lack of sufficient amounts of pure EVs. Here we report a robust and reproducible procedure to isolate EVs from Caenorhabditis elegans with yields similar to those obtained from human cell culture. Through nanoparticle tracking, transmission electron microscopy, flow cytometry, mass spectrometry, RNAseq, and immunoaffinity analysis we provide the first ever detailed characterization of C. elegans EV composition and demonstrate that C. elegans EVs share fundamentally similar properties with their .

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

“…Our work establishes C. elegans as a discovery platform for animal EV biology. We obtained a much greater depth of C. elegans EV protein identification than in previous studies [72,73] via use of a mixed-stage C. elegans population with males and hermaphrodites, enrichment via buoyant density centrifugations, and direct visualization of GFP-labeled EV fractions of interest. The proteogenomic mining approach that we applied to EV cargo candidates lead to the discovery of four novel ciliary EV cargoes.…”

Functional and Cognitive Decline Is Associated With Increased Endothelial Cell Inflammation and Platelet Activation: Liquid Biopsy of Microvesicles in Community- Dwelling Octogenarians

“…In fact, senescent cells have been shown to have a proinflammatory secretome ( Eitan et al, 2017 ; Takasugi, 2018 ) with increased release of MV and overall extracellular vesicles ( Willis et al, 2020 ) with proinflammatory phenotypes ( Alibhai et al, 2020 ; Salminen et al, 2020 ), contributing to age-related comorbidities ( Misawa et al, 2020 ). However, these studies have been performed in in vitro or in in vivo models of aging ( Russell et al, 2020 ; Salminen et al, 2020 ), and human data is lacking.…”

“…However, these studies have been performed in in vitro or in in vivo models of aging (Russell et al, 2020;Salminen et al, 2020), and human data is lacking.…”

RNAs on the Go: Extracellular Transfer in Insects with Promising Prospects for Pest Management

“…These molecules are known to be secreted followed by functional uptake into recipient cells [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In invertebrates, the presence of extracellular RNAs has been demonstrated in arthropods and nematodes, with a limited number of studies demonstrating functional RNA transfer [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Below, we review the current knowledge on extracellular RNAs in insects, establishing the distinct levels of this communication: intercellular/intraindividual, interindividual, interspecies, and interkingdom (insect–plant).…”

“…Since then, a myriad of reports indicate EV-mediated intercellular communication in mammals [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 204 , 205 , 206 , 207 , 208 , 209 ]. Currently, increasing evidence points towards the ubiquitous presence of RNA-containing EVs in animals, as suggested by studies in the nematodes C. elegans [ 57 , 58 , 69 , 76 ], Heligmosomoides polygyrus , Litomosoides sigmodontis [ 77 ], Brugia malayi [ 78 ], H. bakeri, and Trichuris muris [ 80 ]; in the ticks Ixodes Ricinus and Haemaphysalis longicornis [ 59 , 82 ]; as well as in the red swamp crayfish, Procambarus clarkia [ 81 ]. Also in insects, several reports from recent years suggest the involvement of EVs in a common mechanism for functional RNA transfer between cells.…”