Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (3): 608-617.doi: 10.4103/1673-5374.320999

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Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms

Hui-Min Xie1, 2, #, Xing Su3, #, Feng-Yuan Zhang4, #, Chao-Lun Dai4, Rong-Hua Wu1, Yan Li1 , Xiao-Xiao Han1, Xing-Mei Feng2, Bin Yu1, Shun-Xing Zhu5, *, Song-Lin Zhou1, *#br#   

  1. 1Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 2Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 3Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 4Medical College of Nantong University, Nantong, Jiangsu Province, China; 5Laboratory Animals Center, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-03-15 Published:2021-10-15
  • Contact: Shun-Xing Zhu, PhD, zsx@ntu.edu.cn; Song-Lin Zhou, PhD, songlin.zhou@ntu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81870975 (to SLZ); and Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province of China, No. 202010304034Z (to FYZ).

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Abstract: Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018.

Key words: astrocyte, bioinformatics analysis, central nervous system, exosomes, microglia, neurodegenerative disease, RNA transcriptomics, UBB

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