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

Fengbo Zhao,Qian Shao,Xiufang Lv,Yufeng Sun,Peng Lu,Li He,Zixing Chen,Jing Li,Yuhua Ji,Juling Ji,Li Cheng,Qiuhong Ji

doi:10.1038/s41598-020-61098-9

Abstract

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, we 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, our 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.

Highlights

Serum small extracellular vesicles have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content
Nanoparticle tracking analyses (NTA) showed that the diameter of the exosome-enriched extracellular vesicles (EVs) ranged from 30–150 nm, which is consistent with the typical size of previously reported endocytic origin EVs (Fig. 1B)
In regarding to the three species, the size of human serum small extracellular vesicles (sEVs) was the largest, followed by the sEVs isolated from rat serum, while those from mouse serum was the smallest (Fig. 1B), and compared with human and rat serum, more sEV particles were obtained from mouse serum (Fig. 1B)

Summary

Introduction

Serum small extracellular vesicles (sEVs) have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content. Our 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. Many studies addressing the diagnostic or therapeutic potential of serum exosomal miRNAs have been carried out with mice or rats models[5,6,7], but to what extent the mouse and rat serum exosomal contents can resemble those of humans remains unclear. For the first time, the current study compared the small RNAs contents between different species as well as small RNAs contents inside and outside of serum exosomes and to provide clues for future studies on serum exosomal small RNAs

Methods

Results

Conclusion