Comprehensive gene expression analysis of human embryonic stem cells during differentiation into neural cells.

Comprehensive gene expression analysis of human embryonic stem cells during differentiation into neural cells.
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DOI:
10.1371/journal.pone.0022856
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Salekdeh GH
Salekdeh GH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fathi A;Hatami M;Hajihosseini V;Fattahi F;Kiani S;Baharvand H;Salekdeh GH

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对分化为神经细胞的人类胚胎干细胞(hESC)进行全球基因表达分析将有助于进一步确定人类神经发生的分子机制。我们进行了全面的转录组分析hESC分化在三个不同阶段:早期神经分化,神经外胚层,分化的神经元。我们确定并验证了时间依赖性基因表达模式,并表明基因表达模式反映了早期ESC分化。一系列基因在初级外胚层谱系中诱导,然后在分化的神经元中诱导,构成已知和新基因的连续波。通路分析揭示了神经分化过程中包括NOTCH、mTOR和Toll样受体(TLR)在内的几种信号通路成员的动态表达模式。相互作用网络分析显示,TGFβ家族基因,包括LEFTY 1,ID 1和ID 2,可能是神经外胚层增殖和维持的关键参与者。总的来说,这些结果增强了我们对神经承诺和分化的分子动力学的理解。
Global gene expression analysis of human embryonic stem cells (hESCs) that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcripteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm, and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. An interaction network analysis revealed that the TGFβ family of genes, including LEFTY1, ID1 and ID2, are possible key players in the proliferation and maintenance of neural ectoderm. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation.
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