Canonical genetic signatures of the adult human brain.
Canonical genetic signatures of the adult human brain.
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DOI：
10.1038/nn.4171
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发表时间：
2015-12
影响因子：
25
通讯作者：
Lein E
中科院分区：
文献类型：
--
作者：
Hawrylycz M;Miller JA;Menon V;Feng D;Dolbeare T;Guillozet-Bongaarts AL;Jegga AG;Aronow BJ;Lee CK;Bernard A;Glasser MF;Dierker DL;Menche J;Szafer A;Collman F;Grange P;Berman KA;Mihalas S;Yao Z;Stewart L;Barabási AL;Schulkin J;Phillips J;Ng L;Dang C;Haynor DR;Jones A;Van Essen DC;Koch C;Lein E
人类大脑的结构和功能是高度定型的，这意味着一个保守的分子程序负责大脑的发育、细胞结构和功能。我们应用了一种基于相关性的“差分稳定性”（DS）指标来评估6个个体大脑中132个结构的基因表达模式的可重复性，揭示了中尺度遗传组织。最高的DS基因具有高度的生物学相关性，具有丰富的脑相关生物学注释、疾病关联、药物靶点和文献引用。使用高DS基因，我们鉴定了32个解剖学上多样化和可重复的基因表达特征，它们代表了不同的细胞类型、细胞内成分和/或与神经发育和神经退行性疾病的关联。与非神经元网络相比，神经元相关网络中的基因在人和小鼠之间的保存率更高；然而，许多不同模式的基因在物种之间的调节中表现出巨大的变化。最后，新皮层中高度一致的转录结构与静息状态功能连接相关，表明保守基因表达与功能相关回路之间存在联系。
The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry.