Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes
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Significance: The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs), proposed to mediate cell–cell communication in patho/physiological conditions. Although heterogeneity of EVs has become obvious, as highlighted recently by the International Society for Extracellular Vesicles, the field is lacking specific tools to distinguish EVs of different intracellular origins, and thus probably different functions. Here, thanks to a comprehensive comparison of different types of EVs isolated from a single cell type, we define proteins generically present in EVs, small EV-specific and -excluded ones, and a few specific of endosome-derived exosomes or nonexosomal small EVs. This work will allow proper evaluation of the molecular mechanisms of biogenesis and secretion and the respective functions of subtypes of EVs.
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The results imply that CD81-containing EVs, multivesicular bodies, and CD9-positive small EVs derived from the plasma membrane could accumulate in the DNs.
“The results imply that CD81-containing EVs, multivesicular bodies, and CD9-positive small EVs derived from the plasma membrane could accumulate in the DNs [39, 44].”
From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [39]
The Results (p. 6) suggest that CD9-only small EVs probably form at the plasma membrane or early endocytic locations, and the Discussion (p. 8) links tetraspanin-bearing small EVs to the endosomal pathway. The paper does not establish that CD81-containing EVs specifically originate in multivesicular bodies or that any of these structures accumulate in DNs. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMost mitochondrial components have been reported to fractionate in larger EVs by proteomic analysis.
“Most mitochondrial components have been reported to fractionate in larger EVs by proteomic analysis [395].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [395]
The Results (p. 4) report enrichment of mitochondrial proteins in the F5-10K fraction, and the Discussion (p. 8) places mitofilin and possibly other mitochondrial proteins in large and medium-sized EVs rather than small EVs. The paper does not establish that most mitochondrial components fractionate into larger EVs; its analysis concerns EVs from human dendritic cells. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHeterogeneity of EV fractions was confirmed by probing for different vesicular protein markers.
“Heterogeneity of these different fractions was confirmed by probing for different vesicular protein markers that are present in all types of EVs and larger vesicle fractions (Flotillin-1) (Kowal et al., 2016), those typically associated with exosomes and absent in 2,000 × g (ALIX and TSG101), and GAPDH found to be enriched in the 2,000 × g and cellular fraction (McNamara et al., 2018).”
From Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21 (2019) · cites this paper as Kowal et al., 2016
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- Authors
- Kowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal-Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Théry, C.
- Affiliations
- Inserm (FR)
- Université Paris Sciences et Lettres (FR)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-02-08
- Volume
- 113
- Issue
- 8
- Pages
- E968-77
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4776515
- OpenAlex
- W2259481044
- Cited by
- 3,426
- References
- 55
- Citations by year
- 2026: 247 · 2025: 296 · 2024: 336 · 2023: 322 · 2022: 455 · 2021: 454 · 2020: 444 · 2019: 312 · 2018: 278 · 2017: 213 · 2016: 63 · 2013: 1
- FWCI
- 150.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043)
- Association pour la Recherche sur le Cancer (SL220120605293)
- Fondation pour la Recherche Médicale (DGE 20121125630)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- extracellular vesicles, exosomes, dendritic cells, exosomal biomarkers, CD63, CD81, CD9, proteomic profiling, vesicle heterogeneity
- MeSH terms
- Humans, Membrane Proteins, Biomarkers, Antigens, CD, HSP70 Heat-Shock Proteins, Proteomics, Cell-Derived Microparticles
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