Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.
Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.
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DOI：
10.1038/sdata.2017.61
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发表时间：
2017-05-09
期刊：
影响因子：
9.8
通讯作者：
Roopra A
中科院分区：
文献类型：
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作者：
Dingledine R;Coulter DA;Fritsch B;Gorter JA;Lelutiu N;McNamara J;Nadler JV;Pitkänen A;Rogawski MA;Skene P;Sloviter RS;Wang Y;Wadman WJ;Wasterlain C;Roopra A
神经系统或精神疾病的整体表达谱已经被实验室、动物模型、取样的组织和实验平台之间的变异性所混淆，结果是很少有基因表现出一致的表达变化。我们试图尽量减少这些混乱，汇集齿状颗粒细胞的转录谱从164只大鼠在7个实验室，使用三个癫痫持续状态（SE）癫痫模型（匹鲁卡品，红藻氨酸盐，自我持续SE），加上杏仁核点燃。在每种癫痫模型中，在癫痫发生过程早期的四个时间点从六只大鼠的激光捕获的齿状颗粒细胞中收获RNA，并且从两个独立的实验室收集每个啮齿动物模型中的数据，除了SSSE。在三个SE模型中的差异表达的转录物的层次聚类揭示了SE后1天分离的对照和SE大鼠之间的完全分离。然而，SE模型中基因表达变化的一致性在实验室之间仅为26-38%，在模型之间为4.5%，验证了联盟方法。在实验室中具有异常高度可变的对照表达的转录本为低功率研究提供了“红鲱鱼”列表。
Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26–38% between laboratories, and 4.5% among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a ‘red herring’ list for low-powered studies.