中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 103-111.doi: 10.4103/1673-5374.264460

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

利用生物信息学分析鉴定斑马鱼脊髓损伤后轴突再生中关键候选基因和通路

  

  • 出版日期:2020-01-15 发布日期:2020-05-20
  • 基金资助:

    国家自然科学基金国家重点项目(81330042)；国家自然科学基金国际合作项目(81620108018)。

Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish

Jia-He Li1, Zhong-Ju Shi1, Yan Li1, Bin Pan2, Shi-Yang Yuan1, Lin-Lin Shi1,Yan Hao1, Fu-Jiang Cao1, Shi-Qing Feng1, 3   

  1. 1 Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
    2 Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
    3 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
  • Online:2020-01-15 Published:2020-05-20
  • Contact: Shi-Qing Feng, PhD,sqfeng@tmu.edu.cn.
  • Supported by:
    This work was supported by the State Key Program of National Natural Science Foundation of China, No. 81330042 (to SQF); the
    International Cooperation Program of the National Natural Science Foundation of China, No. 81620108018 (to SQF).

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摘要：

斑马鱼和人类的基因组具有较高的同源性，但不同的是，斑马鱼在脊髓损伤后的6-8周可以出现神经细胞的再生及增殖，并且可以实现神经功能的恢复。为了分析斑马鱼脊髓损伤后可再生轴突的神经元及无轴突再生的神经元之间的差异基因，进而进一步探讨斑马鱼脊髓损伤后轴突再生的关键基因和通路，实验应用生物信息学方法在Gene Expression Omnibus(GEO)数据库中应用在线工具GEO2R分析斑马鱼基因芯片GSE56842，筛选出差异表达基因，对差异表达基因进行功能富集分析及蛋白互作网络分析，筛选可能在斑马鱼及哺乳动物脊髓损伤后发挥修复作用的基因及通路。结果发现：(1)实验共得到显著差异表达基因636个，其中在轴突再生神经元中上调的差异表达基因为255个，下调差异表达基因为和381个，实验还获得了GO和KEGG富集结果；(2)蛋白互作结果显示，互作网络共包含480个节点基因和1976个节点连接；(3)试验还得到相关性最高的10个节点基因及得分最高的2个互作模块；(4)试验结果还显示，血影蛋白可能具有促进斑马鱼脊髓损伤后轴突再生的作用，而转化生长因子β信号可能具有抑制斑马鱼脊髓损伤后修复的作用；(5)局灶粘连或紧密连接可能在斑马鱼脊髓损伤后一些细胞如许旺细胞或神经祖细胞的迁移和增殖等方面发挥重要的作用；(6)实验利用生物信息学分析鉴定了斑马鱼脊髓损伤后轴突再生中关键候选基因和通路，为哺乳动物脊髓损伤的治疗提供了有价值的研究靶点。

orcid: 0000-0001-9437-7674 (Shi-Qing Feng)

关键词: 斑马鱼, 脊髓损伤, 轴突再生, 差异表达基因, 生物信息学分析, 基因本体, KEGG信号通路, 蛋白互作网络, 血影蛋白, 转化生长因子β信号

Abstract: Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6–8 weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals.

Key words: axonal regeneration, differentially expressed genes, focal adhesions, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes,
neural regeneration, protein-protein interaction network, signaling pathway, spectrin, tight junctions, transforming growth factor beta, Wnt signaling pathway