中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (3): 608-617.doi: 10.4103/1673-5374.320999

• 原著:退行性病与再生 • 上一篇    下一篇

星形胶质细胞和小胶质细胞外泌体RNA深度测序：神经退行性病变机制的意义

  

  • 出版日期:2022-03-15 发布日期:2021-10-15

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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摘要：

胶质细胞在信号传导、能量代谢、细胞外离子稳态和中枢神经系统神经保护中起重要的作用；然而能详细阐释神经胶质细胞外泌体对中枢神经系统健康和疾病潜在影响的研究则较少见。实验以深度RNA转录组测序鉴定星形胶质细胞和小胶质细胞外泌体中的表达基因。（1）KEGG分析结果表明，来源于星形胶质细胞和小胶质细胞的外泌体中富集的通路与阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病的有关。GO分析显示星形胶质细胞外泌体特异性富集的基因参与细胞外泌体、线粒体、生长因子活性，而小胶质细胞外泌体特异性富集的基因参与外泌体和线粒体相关功能；（2）蛋白相互作用网络结合中枢基因筛选的结果显示，星形胶质细胞外泌体更多通过代谢平衡和泛素依赖蛋白平衡影响神经退行性疾病的差异，而小胶质细胞外泌体更多通过免疫炎症和氧化应激影响神经退行性疾病。虽然两者存在明显差异，但都与UBB、HSPA8等中枢基因有关。其中，UBB可能在神经退行性疾病中发挥免疫调节、炎症抑制、蛋白分解代谢、细胞内蛋白质转运、外泌体和氧化应激等多重调节的关键作用；（3）实验结果揭示了神经胶质细胞外泌体在神经退行性疾病中的临床意义。实验于2018年1月2日经南通大学动物伦理委员会批准（批准号S20180102-152）。

https://orcid.org/0000-0001-8598-0922 (Song-Lin Zhou)

关键词: 小胶质细胞, 星形胶质细胞, 外泌体, RNA转录组学, 中枢神经系统, 神经退行性疾病, UBB, 生物信息学分析

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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