Spatio-temporal transcriptome of the human brain.
Spatio-temporal transcriptome of the human brain.
复制标题
DOI：
10.1038/nature10523
复制
发表时间：
2011-10-26
期刊：
影响因子：
64.8
通讯作者：
Sestan, Nenad
中科院分区：
文献类型：
--
作者：
Kang, Hyo Jung;Kawasawa, Yuka Imamura;Cheng, Feng;Zhu, Ying;Xu, Xuming;Li, Mingfeng;Sousa, Andre M. M.;Pletikos, Mihovil;Meyer, Kyle A.;Sedmak, Goran;Guennel, Tobias;Shin, Yurae;Johnson, Matthew B.;Krsnik, Zeljka;Mayer, Simone;Fertuzinhos, Sofia;Umlauf, Sheila;Lisgo, Steven N.;Vortmeyer, Alexander;Weinberger, Daniel R.;Mane, Shrikant;Hyde, Thomas M.;Huttner, Anita;Reimers, Mark;Kleinman, Joel E.;Sestan, Nenad
在这里，我们报告的全基因组外显子水平的转录组数据的生成和分析，包括小脑皮质，丘脑，纹状体，杏仁核，海马，和11个地区的新皮层的16个大脑区域。该数据集是从57个死后人类大脑的一个或两个半球收集的1，340个组织样本中生成的，这些样本从胚胎发育到成年后期，代表了多个种族的男性和女性。我们还对250万个SNP进行了基因分型，并评估了所有供体的拷贝数变异。发现大约86%的蛋白质编码基因使用严格的标准表达，并且其中超过90%在整个转录本或外显子水平上跨区域和/或时间差异调节。这些时空差异的大部分发生在出生前，其次是在出生后的寿命期间区域转录组之间的相似性增加。基因被组织成功能不同的共表达网络，性别差异存在于基因表达和外显子的使用。最后，我们展示了这些结果如何可以用来描绘与神经发育过程，细胞类型，神经递质系统，自闭症和精神分裂症相关的基因的轨迹，以及发现SNPs和时空基因表达之间的关联。这项研究提供了有关时空人脑转录组的全面、公开的数据集，并对人类神经发育的转录基础提供了新的见解。
Here we report the generation and analysis of genome-wide exon-level transcriptome data from 16 brain regions comprising the cerebellar cortex, mediodorsal nucleus of the thalamus, striatum, amygdala, hippocampus, and 11 areas of the neocortex. The dataset was generated from 1,340 tissue samples collected from one or both hemispheres of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genotyping of 2.5 million SNPs and assessed copy number variations for all donors. Approximately 86% of protein-coding genes were found to be expressed using stringent criteria, and over 90% of these were differentially regulated at the whole transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occurred before birth, followed by an increase in the similarity among regional transcriptomes during postnatal lifespan. Genes were organized into functionally distinct co-expression networks, and sex differences were present in gene expression and exon usage. Finally, we demonstrate how these results can be used to profile trajectories of genes associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia, as well as to discover associations between SNPs and spatiotemporal gene expression. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.
登录
查看更多内容
剪接的组织特异性遗传控制：对复杂性状的研究的影响。
影响因子：
9.8
作者：
Heinzen EL;Ge D;Cronin KD;Maia JM;Shianna KV;Gabriel WN;Welsh-Bohmer KA;Hulette CM;Denny TN;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
16.2
作者：
Lehtinen MK;Zappaterra MW;Chen X;Yang YJ;Hill AD;Lun M;Maynard T;Gonzalez D;Kim S;Ye P;D'Ercole AJ;Wong ET;LaMantia AS;Walsh CA
通讯作者：
Walsh CA
DOI：
10.1073/pnas.0806791105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Kwan, Kenneth Y.;Lam, Mandy M. S.;Sestan, Nenad
通讯作者：
Sestan, Nenad
影响因子：
2.4
作者：
Ip, Bui K.;Wappler, Ilka;Bayatti, Nadhim
通讯作者：
Bayatti, Nadhim
影响因子：
16.2
作者：
Hevner, RF;Shi, LM;Rubenstein, JLR
通讯作者：
Rubenstein, JLR