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Comparative Analyses of Human Exosome Proteomes

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Abstract

Exosomes are responsible for cell-to-cell communication and serves as a valuable drug delivery vehicle. However, exosome heterogeneity, non-standardized isolation methods and proteomics/bioinformatics approaches limit its clinical applications. To better understand exosome heterogeneity, biological function and molecular mechanism of its biogenesis, secretion and uptake, techniques in proteomics or bioinformatics were applied to investigate human embryonic kidney cell (293T cell line)-derived exosome proteome and enable an integrative comparison of exosomal proteins and protein-protein interaction (PPI) networks of eleven exosome proteomes extracted from diverse human samples, including 293T (two datasets), dermal fibroblast, mesenchymal stem cell, thymic epithelial primary cell, breast cancer cell line (MDA-MB-231), patient neuroblastoma cell, plasma, saliva, serum and urine. Mapping of exosome biogenesis/secretion/uptake-related proteins onto exosome proteomes highlights exosomal origin-specific routes of exosome biogenesis/secretion/uptake and exosome-dependent intercellular communication. The finding provides insight into comparative exosome proteomes and its biogenesis, secretion and uptake, and potentially contributes to clinical applications.

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Data Availability

The authors declare that the data that supports the findings of this study are available in the supplementary material of this article.

Abbreviations

ESCRT:

endosomal sorting complexesrequired for transport

GDDA:

Graphlet Degree Distribution agreement

HDF:

human dermal fibroblast

HEK:

human embryonic kidney

HMSC:

human mesenchymal stem cell

HTEC:

human thymic epithelial primary cell

MS:

mass spectrometry

MVB:

multivesicular body

PPI:

protein-protein interaction

RLIs:

receptor-ligand interactions

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant numbers 31470716, 31000323 and 31070672) and the Natural Science Foundation of Jiangsu Province (grant number BK20131272).

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Author notes

  1. Hao Yang, Haiyang Zhang and Hongwei Gu these authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 210023, Jiangsu, P.R. China

    Hao Yang, Haiyang Zhang, Hongwei Gu, Jin Wang, Junfeng Zhang, Ke Zen & Donghai Li

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  1. Hao Yang
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Correspondence to Donghai Li.

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Yang, H., Zhang, H., Gu, H. et al. Comparative Analyses of Human Exosome Proteomes. Protein J 42, 365–373 (2023). https://doi.org/10.1007/s10930-023-10100-0

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