Quantitative transcriptional neuroanatomy of the rat hippocampus: evidence for wide-ranging, pathway-specific heterogeneity among three principal cell layers.
Quantitative transcriptional neuroanatomy of the rat hippocampus: evidence for wide-ranging, pathway-specific heterogeneity among three principal cell layers.
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大鼠海马的定量转录神经解剖学：三个主要细胞层之间的广泛，途径特异性异质性的证据。
DOI：
10.1002/hipo.20502
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发表时间：
2009-03
期刊：
影响因子：
3.5
通讯作者：
Dingledine, Raymond
中科院分区：
文献类型：
--
作者：
Greene, James G.;Borges, Karin;Dingledine, Raymond
我们使用激光捕获显微切割和微阵列杂交来表征大鼠海马三个主要神经元层的基因表达。相关性和聚类分析表明，所有三个层很容易区分彼此的基因表达谱的基础上。齿状颗粒和锥体细胞层之间存在更大的基因表达差异，反映了这些细胞群体之间的表型和本体差异。值得注意的是，超过45%的表达转录物的水平在三个神经元群体之间存在显著差异，其中超过三分之一（> 1，000个转录物）在层之间至少有2倍的差异。甚至CA1和CA3锥体细胞层在转录水平上也有显著差异，单独的分析表明，近20%的转录本在它们之间差异表达。只有少量的转录本是特定的海马细胞层，这表明功能差异更可能是次要的广泛的表达差异，而不是非常大的差异，在一些基因的适度幅度。转录丰度的分类分析显示，协调一致的差异，在基因表达的三个细胞层之间的特定的细胞途径。例如，编码参与葡萄糖代谢的蛋白质的转录本在CA3锥体层中表达最高，这可能反映了这些神经元的潜在代谢率更高，并部分解释了它们对糖尿病诱导的损伤的脆弱性。相反，转录相关的MAP激酶信号通路和转录调节活性是突出的齿状颗粒细胞层，这可能有助于其抵抗损害癫痫发作后的活动，通过定位这些神经元，以响应外部刺激，通过改变转录。两者合计，这些数据表明，独特的生理特性的主要细胞层，如神经元的活动，神经元的可塑性，和神经变性的脆弱性，反映在大量的海马内的转录异质性。
We have used laser-capture microdissection and microarray hybridization to characterize gene expression in the three principal neuron layers of rat hippocampus. Correlative and clustering analyses revealed all three layers to be easily differentiated from one another based on gene expression profile alone. A greater disparity in gene expression exists between dentate granule and pyramidal cell layers, reflecting phenotypic and ontological differences between those cell populations. Remarkably, the level of more than 45% of expressed transcripts was significantly different among the three neuron populations, with more than a third of those (>1,000 transcripts) being at least 2-fold different between layers. Even CA1 and CA3 pyramidal cell layers were dramatically different on a transcriptional level with a separate analysis indicating that nearly 20% of transcripts are differentially expressed between them. Only a small number of transcripts were specific for a given hippocampal cell layer, suggesting that functional differences are more likely secondary to wide-ranging expression differences of modest magnitude rather than very large disparities in a few genes. Categorical analysis of transcript abundance revealed concerted differences in gene expression among the three cell layers referable to specific cellular pathways. For instance, transcripts encoding proteins involved in glucose metabolism are most highly expressed in the CA3 pyramidal layer, which may reflect an underlying greater metabolic rate of these neurons and partially explain their exquisite vulnerability to seizure-induced damage. Conversely, transcripts related to MAP kinase signaling pathways and transcriptional regulator activity are prominent in the dentate granule cell layer, which could contribute to its resistance to damage following seizure activity by positioning these neurons to respond to external stimuli by altering transcription. Taken together, these data suggest that unique physiological characteristics of major cell layers, such as neuronal activity, neuronal plasticity, and vulnerability to neurodegeneration, are reflected in substantial transcriptional heterogeneity within the hippocampus.
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影响因子：
3
作者：
Beisvag V;Jünge FK;Bergum H;Jølsum L;Lydersen S;Günther CC;Ramampiaro H;Langaas M;Sandvik AK;Laegreid A
通讯作者：
Laegreid A
影响因子：
5.3
作者：
Borges, K;Gearing, M;Dingledine, R
通讯作者：
Dingledine, R
影响因子：
3.8
作者：
Garrido, YCS;Sanabria, ERG;Naffah-Mazzacoratti, MG
通讯作者：
Naffah-Mazzacoratti, MG
影响因子：
2.5
作者：
ALTMAN, J;BAYER, SA
通讯作者：
BAYER, SA
影响因子：
7.6
作者：
Kodama, M;Russell, DS;Duman, RS
通讯作者：
Duman, RS