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Identification of neuron-related genes for cell therapy of neurological disorders by network analysis

基于芯片数据的神经分化基因网络互作分析为神经系统疾病的细胞疗法提供基础

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Abstract

Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1248 genes were up-regulated and 1273 were down-regulated in neurons compared with BMSCs. Gene Ontology functional enrichment, protein-protein interaction networks, functional modules, and hub genes were analyzed using DAVID, STRING 10, BiNGO tool, and Network Analyzer software, revealing that nine hub genes, Nrcam, Sema3a, Mapk8, Dlg4, Slit1, Creb1, Ntrk2, Cntn2, and Pax6, may play a pivotal role in neuronal differentiation from BMSCs. Seven genes, Dcx, Nrcam, Sema3a, Cntn2, Slit1, Ephb1, and Pax6, were shown to be hub nodes within the neuronal development network, while six genes, Fgf2, Tgfβ1, Vegfa, Serpine1, Il6, and Stat1, appeared to play an important role in suppressing neuronal differentiation. However, additional studies are required to confirm these results.

摘要

目的

通过筛选差异基因,获得控制骨髓间充质干细胞 向神经细胞分化及神经发育的中心基因,为治疗 神经系统疾病提供参考。

方法

从基因表达综合数据库(Gene Expression Omnibus database)中获得芯片数据,利用生物信息学软件 筛选差异基因,并对差异基因进行GO 功能富集、 蛋白互作网络分析和中心基因分析。

结论

通过分析,初步推测Nrcam、Sema3a、Mapk8、 Dlg4、Slit1、Creb1、Ntrk2、Cntn2 和Pax6 等中 心基因在调控骨髓间充质干细胞向神经细胞的 分化中发挥重要作用;Dcx、Nrcam、Sema3a、 Cntn2、Slit1、Ephb1 和Pax6 等中心基因在神经 发育过程中发挥作用;Fgf2、Tgfβ1、Vegfa、 Serpine1、Il6 和Stat1 等中心基因在抑制神经分化 过程中发挥作用。

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Authors and Affiliations

  1. Department of Biology, Hebei North University, Zhangjiakou, 075029, China

    Li-ning Su, Xiao-qing Song, Hui-ping Wei & Hai-feng Yin

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  1. Li-ning Su
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Correspondence to Hui-ping Wei.

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Project supported by the Key Project of Hebei North University (No. 120177) and the Science and Technology Research Project of Hebei Province Department Institutions of Higher Learning (No. Z2015047), China

Electronic supplementary materials: The online version of this article (http://dx.doi.org/10.1631/jzus.B1600109) contains supplementary materials, which are available to authorized users

ORCID: Li-ning SU, http://orcid.org/0000-0001-8118-7601

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Su, Ln., Song, Xq., Wei, Hp. et al. Identification of neuron-related genes for cell therapy of neurological disorders by network analysis. J. Zhejiang Univ. Sci. B 18, 172–182 (2017). https://doi.org/10.1631/jzus.B1600109

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  • DOI: https://doi.org/10.1631/jzus.B1600109

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