Su Li-Ning, Song Xiao-Qing, Wei Hui-Ping, Yin Hai-Feng
Department of Biology, Hebei North University, Zhangjiakou 075029, China.
J Zhejiang Univ Sci B. 2017;18(2):172-182. doi: 10.1631/jzus.B1600109.
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.
已广泛提出将分化为神经元的骨髓间充质干细胞（BMSCs）用于多种神经系统疾病的细胞治疗。因此，了解这种分化背后的分子机制很重要。我们筛选了未成熟神经组织和未处理的BMSCs之间差异表达的基因，以鉴定负责BMSCs向神经元分化的基因。从基因表达综合数据库获得大鼠BMSCs的GSE68243基因微阵列数据和大鼠神经元的GSE18860基因微阵列数据。转录组分析控制台软件显示，与BMSCs相比，神经元中有1248个基因上调，1273个基因下调。使用DAVID、STRING 10、BiNGO工具和网络分析仪软件对基因本体功能富集、蛋白质-蛋白质相互作用网络、功能模块和枢纽基因进行了分析，结果显示九个枢纽基因Nrcam、Sema3a、Mapk8、Dlg4、Slit1、Creb1、Ntrk2、Cntn2和Pax6可能在BMSCs向神经元的分化中起关键作用。七个基因Dcx、Nrcam、sema3a、Cntn2、Slit1、Ephb1和Pax6被证明是神经元发育网络中的枢纽节点，而六个基因Fgf2、Tgfβ1、Vegfa、Serpine1、Il6和Stat1似乎在抑制神经元分化中起重要作用。然而，需要进一步的研究来证实这些结果。
