Abstract
(1) Background: Extracellular vesicles (EVs) are released by most cell types and are implicated in several biological and pathological processes, including multiple sclerosis (MS). Differences in the number and cargo of plasma-derived EVs have been described in MS. In this work, we have characterised the EV RNA cargo of MS patients, with particular attention to circular RNAs (circRNAs), which have attracted increasing attention for their roles in physiology and disease and their biomarker potential. (2) Methods: Plasma-derived EVs were isolated by differential centrifugation (20 patients, 8 controls), and RNA-Sequencing was used to identify differentially expressed linear and circRNAs. (3) Results: We found differences in the RNA type distribution, circRNAs being enriched in EVs vs. leucocytes. We found a number of (corrected p-value < 0.05) circRNA significantly DE between the groups. Nevertheless, highly structured circRNAs are preferentially retained in leukocytes. Differential expression analysis reports significant differences in circRNA and linear RNA expression between MS patients and controls, as well as between different MS types. (4) Conclusions: Plasma derived EV RNA cargo is not a representation of leukocytes’ cytoplasm but a message worth studying. Moreover, our results reveal the interest of circRNAs as part of this message, highlighting the importance of further understanding RNA regulation in MS.
Highlights
For the RNA profiling of Extracellular vesicles (EVs) from multiple sclerosis (MS) patients and healthy controls (HC), we performed an RNAseq of ribosomic RNA (rRNA)-depleted total RNA from plasma-derived EVs of 20 MS patients and eight
When we compared the circRNA profile between relapsing–remitting multiple sclerosis (RR-MS) patients and HC, we found that among the 6575 bona fide circRNAs detected in total, 1731 (28.4%) were exclusively detected in RR-MS samples, whereas 1413 circRNAs (23.2%) were exclusive to HCs (Figure 4A)
Based on the results drawn from the comparison of the transcriptomic profile between EVs and leukocytes, we suggest that the loading of circRNAs into EVs is a regulated process
Summary
Almost all cell types release EVs, both in physiological and pathological conditions, and they can be isolated from plasma and other bodily fluids. They play an essential role in indirect cell-to-cell communication, as their proteins, lipids and nucleic acids can be transferred between cells [1]. This EV-mediated communication has been shown to be implicated in the regulation of a number of biological functions, including immune response [2,3]. They have been related to inflammatory and autoimmune diseases, including multiple sclerosis (MS) [2,4]
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