title: Cells release subpopulations of exosomes with distinct molecular and biological properties.
abstract: Cells release nano-sized membrane vesicles that are involved in intercellular communication by transferring biological information between cells. It is generally accepted that cells release at least three types of extracellular vesicles (EVs): apoptotic bodies, microvesicles and exosomes. While a wide range of putative biological functions have been attributed to exosomes, they are assumed to represent a homogenous population of EVs. We hypothesized the existence of subpopulations of exosomes with defined molecular compositions and biological properties. Density gradient centrifugation of isolated exosomes revealed the presence of two distinct subpopulations, differing in biophysical properties and their proteomic and RNA repertoires. Interestingly, the subpopulations mediated differential effects on the gene expression programmes in recipient cells. In conclusion, we demonstrate that cells release distinct exosome subpopulations with unique compositions that elicit differential effects on recipient cells. Further dissection of exosome heterogeneity will advance our understanding of exosomal biology in health and disease and accelerate the development of exosome-based diagnostics and therapeutics.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.
authors.forename: Eduard
authors.initials: E
authors.lastname: Willms
authors.affiliation: Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SE-171 21, Sweden.
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Johansson
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.|Institute of Technology, University of Tartu, Tartu, 50411, Estonia.
authors.forename: Imre
authors.initials: I
authors.lastname: Mäger
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SE-141 57, Sweden.
authors.forename: K Emelie M
authors.initials: KE
authors.lastname: Blomberg
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
authors.forename: Mariam
authors.initials: M
authors.lastname: Sadik
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.
authors.forename: Amr
authors.initials: A
authors.lastname: Alaarg
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SE-141 57, Sweden.
authors.forename: C I Edvard
authors.initials: CI
authors.lastname: Smith
authors.affiliation: Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SE-171 21, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: Lehtiö
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.|Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SE-141 57, Sweden.
authors.forename: Samir
authors.initials: S
authors.lastname: El Andaloussi
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.
authors.forename: Matthew J A
authors.initials: MJ
authors.lastname: Wood
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom.|Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vader
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice