Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

• Published in: PloS one Vol. 9; no. 11; p. e113116
• Main Authors: Tietje, Ashlee, Maron, Kourtney N., Wei, Yanzhang, Feliciano, David M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.11.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Age; Age Factors; Aged; Aged, 80 and over; Base Sequence; Biology and life sciences; Brain; Cell culture; Cell signaling; Cell-Derived Microparticles - genetics; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - ultrastructure; Central nervous system; Cerebrospinal fluid; Cerebrospinal Fluid - metabolism; Child; Choroid plexus; Choroid Plexus - cytology; Choroid Plexus - metabolism; Coding; Conserved sequence; DNA microarrays; Epithelial cells; Epithelial Cells - metabolism; Exosomes; Exosomes - genetics; Exosomes - metabolism; Exosomes - ultrastructure; Extracellular vesicles; Fluids; Gene sequencing; Heparan sulfate; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; High-Throughput Nucleotide Sequencing; Humans; Immunoblotting; Infant; Infant, Newborn; Lipids; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy; Microscopy, Electron, Transmission; miRNA; Nanoparticles; Non-coding RNA; Nucleic acids; Oligonucleotide Array Sequence Analysis; Physiology; Proteins; Ribonucleic acid; RNA; RNA, Untranslated - cerebrospinal fluid; RNA, Untranslated - genetics; Sequence Homology, Nucleic Acid; Stem cells; Vesicles; United Kingdom > UK; United States > US; South Carolina
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113116

Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development.