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全基因组表达谱的空间模式反映了健康人类大脑的解剖结构和纤维连接结构。

Spatial patterns of genome-wide expression profiles reflect anatomic and fiber connectivity architecture of healthy human brain.

作者信息

Goel Pragya, Kuceyeski Amy, LoCastro Eve, Raj Ashish

机构信息

Department of Computer Science, Cornell University, Ithaca, New York.

出版信息

Hum Brain Mapp. 2014 Aug;35(8):4204-18. doi: 10.1002/hbm.22471. Epub 2014 Feb 22.

Abstract

Unraveling the relationship between molecular signatures in the brain and their functional, architectonic, and anatomic correlates is an important neuroscientific goal. It is still not well understood whether the diversity demonstrated by histological studies in the human brain is reflected in the spatial patterning of whole brain transcriptional profiles. Using genome-wide maps of transcriptional distribution of the human brain by the Allen Brain Institute, we test the hypothesis that gene expression profiles are specific to anatomically described brain regions. In this work, we demonstrate that this is indeed the case by showing that gene similarity clusters appear to respect conventional basal-cortical and caudal-rostral gradients. To fully investigate the causes of this observed spatial clustering, we test a connectionist hypothesis that states that the spatial patterning of gene expression in the brain is simply reflective of the fiber tract connectivity between brain regions. We find that although gene expression and structural connectivity are not determined by each other, they do influence each other with a high statistical significance. This implies that spatial diversity of gene expressions is a result of mainly location-specific features but is influenced by neuronal connectivity, such that like cellular species preferentially connects with like cells.

摘要

揭示大脑中分子特征与其功能、结构和解剖学相关性之间的关系是一个重要的神经科学目标。目前仍不清楚人类大脑组织学研究中所显示的多样性是否反映在全脑转录谱的空间模式中。利用艾伦脑科学研究所绘制的人类大脑转录分布全基因组图谱,我们检验了基因表达谱特定于解剖学描述的脑区这一假设。在这项工作中,我们通过表明基因相似性簇似乎遵循传统的基底 - 皮质和尾 - 嘴侧梯度,证明了情况确实如此。为了全面研究这种观察到的空间聚类的原因,我们检验了一种联结主义假设,即大脑中基因表达的空间模式仅仅反映了脑区之间的纤维束连接性。我们发现,虽然基因表达和结构连接性并非相互决定,但它们确实以高度的统计学显著性相互影响。这意味着基因表达的空间多样性主要是位置特异性特征的结果,但受到神经元连接性的影响,即同类细胞优先与同类细胞连接。

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