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Updated: Dec 2, 2025
Isolation and Analysis of Traceable and Functionalized Extracellular Vesicles from the Plasma and Solid Tissues
Published on: October 17, 2022
EV-origin: Enumerating the tissue-cellular origin of circulating extracellular vesicles using exLR profile.
Yuchen Li1,2, Xigan He3, Qin Li1,2
1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
We developed EV-origin, a novel method to quantify the tissue and cell origins of circulating extracellular vesicles (EVs) in plasma. This approach aids in understanding disease states and developing liquid biopsy applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Genomics
Background:
- Extracellular vesicles (EVs) are circulating biological nanoparticles originating from various body cells.
- Characterizing the cellular source of EVs offers insights into physiological and pathological states.
- The precise proportional contribution of different tissues to circulating EVs remains largely unquantified.
Purpose of the Study:
- To develop a computational method for quantifying the tissue-cellular source contribution of plasma extracellular vesicles.
- To enable the enumeration of specific cell types and tissue subsets contributing to circulating EVs.
- To establish a traceable landscape of plasma EV origins in healthy and diseased individuals.
Main Methods:
- Development of the EV-origin computational approach for digital EV quantification.
- Utilizing plasma extracellular vesicle long RNA sequencing (exLR-seq) profiles as input.
- Employing gene expression signatures and a robust deconvolution algorithm to determine relative tissue proportions.
Main Results:
- EV-origin successfully predicted the relative abundance of seven hematopoietic cell types and sixteen solid tissue subsets.
- An integrated landscape of plasma EV traceability was depicted for healthy individuals.
- Aberrant liver fractions in plasma EVs correlated with hepatic disease development and progression, distinguishing HCC patients from healthy controls.
Conclusions:
- The EV-origin approach provides a method to decipher the complex heterogeneity of tissue-cellular origins in circulating EVs.
- Plasma EV liver fraction shows potential as a diagnostic indicator for hepatic diseases, including hepatocellular carcinoma (HCC).
- This methodology could advance the development of exLR-seq-based liquid biopsy applications.
