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成人嗅球和胚胎神经干细胞的基因表达谱提示了不同的信号通路和表观遗传调控。

Gene expression profile of adult human olfactory bulb and embryonic neural stem cell suggests distinct signaling pathways and epigenetic control.

机构信息

Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.

出版信息

PLoS One. 2012;7(4):e33542. doi: 10.1371/journal.pone.0033542. Epub 2012 Apr 2.

Abstract

Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults.

摘要

采用 RNA 对人类胚胎神经干细胞(hENSC)和成人嗅球源性神经干细胞(OBNSC)进行了全基因表达谱分析,以确定特定于每个细胞谱系的基因表达模式和信号通路。我们已经证明了人类胚胎 NSC 和成人人类 OBNSC 的基因表达谱存在很大差异,但平行培养之间的变异性较小。参与神经管发育和模式形成的基因(ALDH1A2、FOXA2)、祖细胞标记基因(LMX1a、ALDH1A1、SOX10)、神经前体细胞增殖(WNT1 和 WNT3a)、神经塑性蛋白(NPTN)、POU3F1(OCT6)、神经连接蛋白(NLGN4X)、MEIS2 和 NPAS1 的转录本在两种细胞群中均上调。通过基因本体论,在 3875 个研究基因集中有 325 个具有科学差异。在 41 个研究细胞成分(CC)类别中,620 个研究分子功能(MF)类别中有 45 个,2948 个研究生物过程(BP)类别中有 239 个有统计学意义。KEGG 途径分类比较显示,在 171 个研究基因集中,有 75 个通过了 0.005 的显著性阈值。研究了三个已知参与 NS 细胞命运决定的信号通路 Notch、Wnt 和 mTOR 的基因表达水平。转录特征还解释了参与表观遗传修饰的基因的作用。SWI/SNF DNA 染色质重塑复合物家族,包括 SMARCC1 和 SMARCE1,在我们的 OBNSC 中特异性上调,但在 hENSC 中没有上调。控制表观遗传修饰和信号通路的基因表达谱的差异可能表明,在不同的中枢神经系统损伤后,我们研究的两种细胞群体在细胞存活、增殖、迁移和分化方面的治疗潜力存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b39/3317670/1b685611ea3b/pone.0033542.g001.jpg

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