CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs

Sukhbir Kaur; Abdel G Elkahloun; Anush Arakelyan; Lynn Young; Timothy G Myers; Francisco Otaizo-Carrasquero; Weiwei Wu; Leonid Margolis; David D Roberts

doi:10.1038/s41598-018-20936-7

CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs

Sci Rep. 2018 Feb 7;8(1):2577. doi: 10.1038/s41598-018-20936-7.

Authors

Sukhbir Kaur¹, Abdel G Elkahloun², Anush Arakelyan³, Lynn Young⁴, Timothy G Myers⁵, Francisco Otaizo-Carrasquero⁵, Weiwei Wu², Leonid Margolis³, David D Roberts⁶

Affiliations

¹ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20982, USA.
² Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
³ Section of Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20982, USA.
⁴ National Institutes of Health Library, Division of Library Services, Office of Research Services, National Institutes of Health, Bethesda, MD, 20892, USA.
⁵ Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
⁶ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20982, USA. droberts@mail.nih.gov.

Abstract

Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies. These EV subsets have similar sizes but divergent RNA contents. Apart from differences in numbers of nonannotated transcripts, CD63⁺, MHC1⁺, and CD47⁺ EVs have similar overall contents of most noncoding RNA classes, but the relative enrichment of specific RNAs differs. The enrichment of micro-RNAs is highly divergent, and some including miR320a are selectively concentrated in CD47⁺ EVs. Small nucleolar RNAs including SNORD116@ and SNHG10 are also selectively enriched in CD47⁺ EVs, whereas no small nuclear RNAs are enriched in CD47⁺ EVs. Conversely, MHC1⁺ EVs are selectively enriched in a subset of tRNAs including TRE-CTC and TRR-CCG. This heterogeneity in RNA composition suggests multiple sorting mechanisms that direct specific RNAs into subsets of EVs that express specific surface markers.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Biomarkers / metabolism
CD47 Antigen / immunology*
Extracellular Vesicles* / immunology
Extracellular Vesicles* / metabolism
Histocompatibility Antigens Class I / immunology*
Humans
Jurkat Cells
MicroRNAs / metabolism*
RNA, Small Nucleolar / metabolism*
RNA, Transfer / metabolism*
Tetraspanin 30 / immunology*

Substances

Antibodies, Monoclonal
Biomarkers
CD47 Antigen
CD47 protein, human
CD63 protein, human
Histocompatibility Antigens Class I
MicroRNAs
RNA, Small Nucleolar
Tetraspanin 30
RNA, Transfer