Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain
Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain
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DOI：
10.1073/pnas.1222897110
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发表时间：
2013-02-19
影响因子：
11.1
通讯作者：
Price, Nathan D.
中科院分区：
文献类型：
--
作者：
Ko, Younhee;Ament, Seth A.;Price, Nathan D.
为了表征哺乳动物大脑区域细分的基因表达模式，我们整合了成年小鼠艾伦脑图谱中的空间基因表达模式，以及先前发表的转录组分析实验中神经元、星形胶质细胞和少突胶质细胞的细胞类型特异性基因。我们发现，170个神经元特异性转录本的组合空间表达模式揭示了大脑大部分主要分区的惊人清晰和对称的特征。此外，大脑表达空间特征对应于解剖结构，甚至可以反映发育个体发育。星形胶质细胞和少突胶质细胞特异性基因的空间表达谱也揭示了区域差异;这些定义的区域较少，不太明显，但在冠状平面上仍然对称。后续分析表明，基于区域的神经元特异性基因的聚类与以下因素有关：（i）具有受限表达模式的单个基因的组合，（ii）基因功能组相对表达的区域特异性差异，以及（iii）神经元密度的区域差异。来自这些神经元特异性基因中的一些的产物存在于外周血中，提高了它们可以反映疾病或损伤扰动网络的活动并共同作为临床疾病诊断的生物标志物的可能性。
To characterize gene expression patterns in the regional subdivisions of the mammalian brain, we integrated spatial gene expression patterns from the Allen Brain Atlas for the adult mouse with panels of cell type-specific genes for neurons, astrocytes, and oligodendrocytes from previously published transcriptome profiling experiments. We found that the combined spatial expression patterns of 170 neuron-specific transcripts revealed strikingly clear and symmetrical signatures for most of the brain's major subdivisions. Moreover, the brain expression spatial signatures correspond to anatomical structures and may even reflect developmental ontogeny. Spatial expression profiles of astrocyte-and oligodendrocyte-specific genes also revealed regional differences; these defined fewer regions and were less distinct but still symmetrical in the coronal plane. Follow-up analysis suggested that region-based clustering of neuron-specific genes was related to (i) a combination of individual genes with restricted expression patterns, (ii) region-specific differences in the relative expression of functional groups of genes, and (iii) regional differences in neuronal density. Products from some of these neuron-specific genes are present in peripheral blood, raising the possibility that they could reflect the activities of disease-or injury-perturbed networks and collectively function as biomarkers for clinical disease diagnostics.