Functional and evolutionary insights into human brain development through global transcriptome analysis.

Functional and evolutionary insights into human brain development through global transcriptome analysis.
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DOI:
10.1016/j.neuron.2009.03.027
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发表时间:
2009-05-28
期刊:
影响因子:
16.2
通讯作者:
Sestan, Nenad
Sestan, Nenad
中科院分区:
医学1区
文献类型:
--
作者:
Johnson, Matthew B.;Kawasawa, Yuka Imamura;Mason, Christopher E.;Krsnik, Zeljka;Coppola, Giovanni;Bogdanovic, Darko;Geschwind, Daniel H.;Mane, Shrikant M.;State, Matthew W.;Sestan, Nenad

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由于缺乏关于发育中的大脑转录组的全面数据,我们对人类大脑回路的进化、形成和病理破坏的理解受到阻碍。因此,我们对胎儿中期大脑左右两侧的13个区域进行了全基因组、外显子水平的表达分析,发现76%的基因得到表达,其中44%的基因受到差异调节。这些数据揭示了大量特定基因表达和选择性剪接模式,以及与不同区域和神经发育过程相关的共表达网络。与认知专业化特别相关的是,我们描述了前额叶皮层和周裂言语和语言区域的转录景观,这些区域表现出群体水平的全局表达对称性。最后,我们表明差异表达的基因更频繁地与假定的顺式调控元件的人类特异性进化相关。总而言之,这些数据为人类大脑发育和进化的复杂转录和分子基础提供了大量新颖的生物学见解。
Our understanding of the evolution, formation, and pathological disruption of human brain circuits is impeded by a lack of comprehensive data on the developing brain transcriptome. Thus, we have undertaken whole-genome, exon-level expression analysis of thirteen regions from left and right sides of the mid-fetal human brain, finding 76% of genes to be expressed, and 44% of these to be differentially regulated. These data reveal a large number of specific gene expression and alternative splicing patterns, as well as co-expression networks, associated with distinct regions and neurodevelopmental processes. Of particular relevance to cognitive specializations, we have characterized the transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas, which exhibit a population-level global expression symmetry. Finally, we show that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements. Altogether, these data provide a wealth of novel biological insights into the complex transcriptional and molecular underpinnings of human brain development and evolution.
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