Transcriptome profiling of human hippocampus dentate gyrus granule cells in mental illness.
Transcriptome profiling of human hippocampus dentate gyrus granule cells in mental illness.
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DOI：
10.1038/tp.2014.9
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发表时间：
2014-03-04
影响因子：
6.8
通讯作者：
Haugen E
中科院分区：
文献类型：
--
作者：
Kohen R;Dobra A;Tracy JH;Haugen E
据我们所知，这项研究首次将全转录组测序（RNA-seq）应用于通过激光捕获显微切割从死后人脑中分离出的细胞。我们研究了 79 名患有精神疾病（精神分裂症、双相情感障碍、重度抑郁症）的受试者和非精神病对照者死后人类海马中齿状回 (DG) 颗粒细胞的转录组。我们表明，RNA-seq 数据分析的归一化方法的选择对结果有很大影响；在我们的实验条件下，非标准标准化方法给出了更好的结果。我们发现了 miR-182 在精神疾病中信号传导被破坏的证据。使用一种利用 microRNA 遗传变异信息来指示主动靶向的新方法证实了这一点。在健康受试者和双相情感障碍患者中，miR-182 高表达基因型的携带者与低表达基因型的携带者具有不同水平的 miR-182 靶基因表达，表明 miR-182 在塑造这些受试者组的 DG 转录组中发挥着积极作用。相比之下，比较重度抑郁症和精神分裂症受试者中不同基因型携带者之间的转录组表明，在这些情况下 DG miR-182 信号丢失。
This study is, to the best of our knowledge, the first application of whole transcriptome sequencing (RNA-seq) to cells isolated from postmortem human brain by laser capture microdissection. We investigated the transcriptome of dentate gyrus (DG) granule cells in postmortem human hippocampus in 79 subjects with mental illness (schizophrenia, bipolar disorder, major depression) and nonpsychiatric controls. We show that the choice of normalization approach for analysis of RNA-seq data had a strong effect on results; under our experimental conditions a nonstandard normalization method gave superior results. We found evidence of disrupted signaling by miR-182 in mental illness. This was confirmed using a novel method of leveraging microRNA genetic variant information to indicate active targeting. In healthy subjects and those with bipolar disorder, carriers of a high- vs those with a low-expressing genotype of miR-182 had different levels of miR-182 target gene expression, indicating an active role of miR-182 in shaping the DG transcriptome for those subject groups. By contrast, comparing the transcriptome between carriers of different genotypes among subjects with major depression and schizophrenia suggested a loss of DG miR-182 signaling in these conditions.
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DOI：
10.1038/npp.2008.172
发表时间：
2009-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.2
作者：
Balu, Darrick T.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
14.9
作者：
Altuvia Y;Landgraf P;Lithwick G;Elefant N;Pfeffer S;Aravin A;Brownstein MJ;Tuschl T;Margalit H
通讯作者：
Margalit H
影响因子：
7
作者：
Ceribelli A;Satoh M;Chan EK
通讯作者：
Chan EK
影响因子：
9.8
作者：
Blackwood, DHR;Fordyce, A;Muir, WJ
通讯作者：
Muir, WJ