RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level.
RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level.
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DOI：
10.1371/journal.pone.0072567
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wu JQ
中科院分区：
文献类型：
--
作者：
Chen K;Deng S;Lu H;Zheng Y;Yang G;Kim D;Cao Q;Wu JQ
脊髓损伤（Spinal cord injury，SCI）是一种严重的神经系统疾病，目前尚无有效的治疗方法。为了全面了解SCI病理学机制，我们应用RNA测序（RNA-Seq）技术来表征小鼠挫伤性SCI后全球基因表达的时间变化。我们对急性和亚急性期（损伤后2天和7天）的组织样本进行测序，并系统地表征转录组，目的是确定SCI病理学中的关键通路和基因。最丰富的功能类别包括“炎症反应”，“神经系统疾病”，“细胞死亡和存活”和“神经系统发育”。最丰富的途径包括LXR/RXR激活和动脉粥样硬化信号传导等。此外，我们开发了一个基于系统的分析框架，以确定急性和亚急性期全球基因网络中的关键决定因素。我们发现的一些候选基因已被证明在SCI中起重要作用，这证明了我们方法的有效性。还有许多基因在SCI中的功能尚未得到很好的研究，可以通过未来的实验进一步研究。我们还将药物基因组学信息纳入我们的分析。在已鉴定的基因中，具有现有药物信息的基因可以容易地在SCI动物模型中进行测试。因此，在这项研究中，我们描述了一个例子，说明如何将全球基因谱转化为识别未来功能测试的感兴趣基因并产生新的假设。此外，RNA-Seq能够识别剪接异构体和估计表达水平，从而为增加药物设计的特异性和减少潜在的副作用提供有用的信息。总之，这些结果提供了一个有价值的参考数据资源，以更好地了解脊髓损伤的过程中的急性和亚急性期。
Spinal cord injury (SCI) is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury) and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology. The top enriched functional categories include “inflammation response,” “neurological disease,” “cell death and survival” and “nervous system development.” The top enriched pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc. Furthermore, we developed a systems-based analysis framework in order to identify key determinants in the global gene networks of the acute and sub-acute phases. Some candidate genes that we identified have been shown to play important roles in SCI, which demonstrates the validity of our approach. There are also many genes whose functions in SCI have not been well studied and can be further investigated by future experiments. We have also incorporated pharmacogenomic information into our analyses. Among the genes identified, the ones with existing drug information can be readily tested in SCI animal models. Therefore, in this study we have described an example of how global gene profiling can be translated to identifying genes of interest for functional tests in the future and generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform identification and the estimation of expression levels, thus providing useful information for increasing the specificity of drug design and reducing potential side effect. In summary, these results provide a valuable reference data resource for a better understanding of the SCI process in the acute and sub-acute phases.
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影响因子：
4.3
作者：
Batada NN;Hurst LD;Tyers M
通讯作者：
Tyers M
影响因子：
3.7
作者：
Adzemovic MZ;Öckinger J;Zeitelhofer M;Hochmeister S;Beyeen AD;Paulson A;Gillett A;Thessen Hedreul M;Covacu R;Lassmann H;Olsson T;Jagodic M
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影响因子：
5.2
作者：
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通讯作者：
Cao, Qilin
DOI：
10.1177/1073858408331372
发表时间：
2009-04
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
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作者：
Darian-Smith C
通讯作者：
Darian-Smith C
影响因子：
82.9
作者：
Demjen, D;Klussmann, S;Martin-Villalba, A
通讯作者：
Martin-Villalba, A