Characterization of serum small extracellular vesicles and their small RNA contents across humans, rats, and mice

Serum small extracellular vesicles (sEVs) have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content. However, the characteristics of human, mouse and rat serum sEVs and their differences in small RNA contents are still unknown. In this study, through nanoparticle tracking analysis and small RNA sequencing, researchers fromthe  Medical School of Nantong University found that human, rat, and mouse serum sEVs exhibited distinct sizes and particle numbers as well as small RNA contents. Serum sEVs contained not only abundant miRNAs but also a large number of tRNA fragments. Most serum miRNAs existed both inside and outside of sEVs but were enriched in sEVs. Common serum sEV miRNAs (188 miRNAs) and species-specific serum sEV miRNAs (265, 58, and 159 miRNAs, respectively) were identified in humans, rats, or mice. The serum sEVs contained miRNAs from tissues and organs throughout the body, with blood cells as the main contributors. In conclusion, these findings confirmed the rationality of exploring serum sEV miRNAs as noninvasive diagnostic markers and revealed great differences in serum sEV small RNAs between humans, rats, and mice. Inadequate attention to these differences and the contribution of blood cells to serum sEV miRNAs could hinder the clinical translation of basic studies.

The expression of miRNAs in serum sEV vs. de-sEV serum,
and the expression of miRNAs in serum sEV between species

 

(A) The venny diagram depicts the common and unique miRNAs identified in serum sEV miRNAs and de-sEV serum miRNAs from human, rat and mouse, respectively. (B) The composition of miRNAs based on the relative expression of serum sEVs vs. sEV-depleted serum, only those miRNAs existed both inside and outside of serum sEV were included. (C) The venny diagram depicts the common and unique miRNAs identified in serum sEV miRNAs from human, rat and mouse. (D) Heat map of hierarchical clustering of the 188 common serum sEV miRNAs between species based on log2 transformed TMP (transcripts per million reads). Each column represents an individual sample, each row represents an individual miRNA. miRNAs were ordered by Pearson correlation and complete linkage. TPM, transcripts per million reads; sEV, small extracellular vesicle; de-sEV, small extracellular vesicle depleted; e, serum small extracellular vesicle; d, small extracellular vesicle depleted serum.