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鉴定成年斑马鱼脊髓损伤后神经元内在生长能力异质性中的关键基因和途径。

Identification of Key Genes and Pathways Involved in the Heterogeneity of Intrinsic Growth Ability Between Neurons After Spinal Cord Injury in Adult Zebrafish.

机构信息

School of Medicine, Nankai University, Tianjin, 300110, China.

Department of Orthopedics, the General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.

出版信息

Neurochem Res. 2019 Sep;44(9):2057-2067. doi: 10.1007/s11064-019-02841-1. Epub 2019 Jul 19.

DOI:10.1007/s11064-019-02841-1
PMID:31325155
Abstract

In the adult central nervous system (CNS), axon regeneration is a major hurdle for functional recovery after trauma. The intrinsic growth potential of an injured axon varies widely between neurons. The underlying molecular mechanisms of such heterogeneity are largely unclear. In the present study, the adult zebrafish dataset GSE56842 were downloaded. Differentially expressed genes (DEGs) were sorted and deeply analyzed by bioinformatics methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed with the DAVID. A DEGs-associated protein-protein interaction network was constructed from the STRING database and visualized with Cytoscape software. In total, 621 DEGs were identified. GO analysis showed that the biological processes of DEGs focused mainly on the Notch signaling pathway, cell differentiation and positive regulation of neuron differentiation. The molecular functions mainly included calcium-transporting ATPase activity and calcium ion binding and structural constituents of the cytoskeleton. The cellular components included the plasma membrane, spectrin, and cytoplasmic and membrane-bound vesicles. KEGG pathway analysis showed that these DEGs were mainly involved in the metabolic pathway and Notch signaling pathway, and subnetworks revealed that genes within modules were involved in the metabolic pathway, Wnt signaling pathway, and calcium signaling pathway. This study identified DEG candidate genes and pathways involved in the heterogeneity of the intrinsic growth ability between neurons after spinal cord injury in adult zebrafish, which could facilitate our understanding of the molecular mechanisms underlying axon regeneration, and these candidate genes and pathways could be therapeutic targets for the treatment of CNS injury.

摘要

在成人中枢神经系统(CNS)中,轴突再生是创伤后功能恢复的主要障碍。受伤轴突的内在生长潜力在神经元之间差异很大。这种异质性的潜在分子机制在很大程度上尚不清楚。本研究下载了成年斑马鱼数据集 GSE56842。通过生物信息学方法对差异表达基因(DEGs)进行排序和深入分析。使用 DAVID 对 DEGs 进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。从 STRING 数据库构建 DEGs 相关的蛋白质-蛋白质相互作用网络,并使用 Cytoscape 软件可视化。共鉴定出 621 个 DEGs。GO 分析表明,DEGs 的生物学过程主要集中在 Notch 信号通路、细胞分化和神经元分化的正调控。分子功能主要包括钙转运 ATP 酶活性和钙离子结合以及细胞骨架的结构成分。细胞成分包括质膜、 spectrin 以及细胞质和膜结合囊泡。KEGG 通路分析表明,这些 DEGs 主要参与代谢途径和 Notch 信号通路,子网络显示模块内的基因参与代谢途径、Wnt 信号通路和钙信号通路。本研究鉴定了成年斑马鱼脊髓损伤后神经元内在生长能力异质性相关的 DEG 候选基因和通路,有助于我们理解轴突再生的分子机制,这些候选基因和通路可能成为 CNS 损伤治疗的靶点。

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本文引用的文献

1
Granulin 1 Promotes Retinal Regeneration in Zebrafish.颗粒蛋白前体 1 促进斑马鱼的视网膜再生。
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The Promising Role of a Zebrafish Model Employed in Neural Regeneration Following a Spinal Cord Injury.斑马鱼模型在脊髓损伤后神经再生中的应用前景。
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Identification of key genes involved in recovery from spinal cord injury in adult zebrafish.成年斑马鱼脊髓损伤恢复过程中关键基因的鉴定
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Identification of Regeneration and Hub Genes and Pathways at Different Time Points after Spinal Cord Injury.脊髓损伤后不同时间点的再生和枢纽基因及通路的鉴定。
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Sox2 regulates Müller glia reprogramming and proliferation in the regenerating zebrafish retina via Lin28 and Ascl1a.Sox2通过Lin28和Ascl1a调节再生斑马鱼视网膜中穆勒胶质细胞的重编程和增殖。
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