The heterogeneity of exosomes has always been a very important point in the field of exosome research. Traditional exosome analysis (e.g., PCR, RNA sequencing) determines the number of transcripts in exosomes by analyzing all exosomes in aggregate. But this approach cannot reveal information about transcripts within individual exosomes. Therefore, it is crucial to explore transcriptome features and heterogeneity at the level of individual exosomes. Single-cell transcriptome sequencing (scT-seq) is a new technique to sequence all transcripts at the single-cell level. scT-seq can not only study gene expression in single cells but also solve the problem of cellular heterogeneity that cannot be solved by sequencing tissue samples. scT-seq makes it possible to analyze the behavior and mechanism of individual cells and their relation with the body. With the in-depth exploration of exosomes, scT-seq can study transcriptomic characteristics and heterogeneity at the level of individual exosomes. In addition, the scT-seq combined analysis of exosome and cell can provide evidence for the source and destination of exosomes. Creative Biolabs can provide single-cell and exosome combined transcriptomics research service, helping customers to more accurately analyze exosomes from the transcriptome level to further develop the potential of exosomes.

Application of Analyzing Individual Exosomes by Single-cell Transcriptome Sequencing

By performing scT-seq on the isolated exosomes, the subgroup classification of exosomes can be obtained according to the differences in transcript levels. A research team analyzed the extracellular vesicles derived from K562 cells and mesenchymal stem cells through scT-seq and found that even the extracellular vesicles derived from the same type of cells are still highly heterogeneous, and can be divided into multiple vesicle subsets with specific transcriptional profiles. These subsets may have specific functions, or several subsets may perform the same communication task. These data suggest that the analysis of individual exosomes by scT-seq can provide a basis for elucidating the action mechanism of exosomes.

Fig. 1 Schematic overview of single-EV transcriptomes analysis workflow. (Luo, 2022)

Advantages of Combined Single-cell Transcriptome Sequencing of Exosomes and Cells

Due to its high-resolution characteristics, scT-seq has incomparable advantages over traditional RNA sequencing in the study of cell heterogeneity and analysis of tissue microenvironmental characteristics. However, there are certain limitations in analyzing the interrelationships between different cells in tissues. Since exosomes are an important medium for cell-to-cell communication, analyzing the transcript characteristics of exosomes in the tissue microenvironment by scT-seq and exosome transcriptomics can provide a basis for revealing the exosome communication network between cell subsets in the microenvironment. In addition, the combined scT-seq analysis of tissue and body fluid-derived exosomes can more accurately help customers mine disease-related biomarkers and further advance exosome-related liquid biopsy.

Fig. 2 Schematic overview of the single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. (Zhang, 2020)

Creative Biolabs has been committed to helping customers discover the various possibilities of exosomes to promote the transformation of exosome applications to the clinic. We can take the most suitable method to extract and identify exosomes from cell supernatants, body fluids, or tissues, and provide you with the most valuable exosome transcript profiles through scT-seq to help you discover the origin of exosomes or potential disease biomarkers. Please contact us to put forward your ideas, our professional team will provide you with the best research plan as soon as possible according to your research purpose.

References

1. Luo, T.; Chen, SY.; et al. Transcriptomic features in a single extracellular vesicle via single-cell RNA sequencing. Small Methods. 2022. 6(11):e2200881.
2. Zhang, M.; Yang, H.; et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. Journal of Hepatology. 2020. 73(5):1118-1130.

• Single-Cell & Exosome Combined Proteomics Research