An anatomically comprehensive atlas of the adult human brain transcriptome.
An anatomically comprehensive atlas of the adult human brain transcriptome.
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DOI：
10.1038/nature11405
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发表时间：
2012-09-20
期刊：
影响因子：
64.8
通讯作者：
Jones, Allan R.
中科院分区：
文献类型：
--
作者：
Hawrylycz, Michael J.;Lein, Ed S.;Guillozet-Bongaarts, Angela L.;Shen, Elaine H.;Ng, Lydia;Miller, Jeremy A.;van de lagemaat, Louie N.;Smith, Kimberly A.;Ebbert, Amanda;Riley, Zackery L.;Abajian, Chris;Beckmann, Christian F.;Bernard, Amy;Bertagnolli, Darren;Boe, Andrew F.;Cartagena, Preston M.;Chakravarty, M. Mallar;Chapin, Mike;Chong, Jimmy;Dalley, Rachel A.;Daly, Barry David;Dang, Chinh;Datta, Suvro;Dee, Nick;Dolbeare, Tim A.;Faber, Vance;Feng, David;Fowler, David R.;Goldy, Jeff;Gregor, Benjamin W.;Haradon, Zeb;Haynor, David R.;Hohmann, John G.;Horvath, Steve;Howard, Robert E.;Jeromin, Andreas;Jochim, Jayson M.;Kinnunen, Marty;Lau, Christopher;Lazarz, Evan T.;Lee, Changkyu;Lemon, Tracy A.;Li, Ling;Li, Yang;Morris, John A.;Overly, Caroline C.;Parker, Patrick D.;Parry, Sheana E.;Reding, Melissa;Royall, Joshua J.;Schulkin, Jay;Sequeira, Pedro Adolfo;Slaughterbeck, Clifford R.;Smith, Simon C.;Sodt, Andy J.;Sunkin, Susan M.;Swanson, Beryl E.;Vawter, Marquis P.;Williams, Derric;Wohnoutka, Paul;Zielke, H. Ronald;Geschwind, Daniel H.;Hof, Patrick R.;Smith, Stephen M.;Koch, Christof;Grant, Seth G. N.;Jones, Allan R.
神经解剖学上精确的全基因组转录分布图是补充基因组序列数据以及关联功能和遗传大脑结构的关键资源。在这里，我们描述了成人大脑转录图谱的生成和分析，包括对两个个体的约 900 个神经解剖学精确细分进行广泛的组织学分析和全面的微阵列分析。转录调控因解剖位置而异，不同区域及其组成细胞类型显示出在个体之间高度保守的强大分子特征。对差异基因表达和基因共表达关系的分析表明，全脑变异强烈反映了主要细胞类别（如神经元、少突胶质细胞、星形胶质细胞和小胶质细胞）的分布。精细解剖细分之间的局部邻域关系与离散的神经元亚型和涉及突触传递的基因相关。新皮质表现出相对均质的转录模式，但具有选择性地与初级感觉运动皮质和丰富的额叶表达相关的独特特征。值得注意的是，新皮质的空间拓扑结构强烈地反映在其分子拓扑结构中——两个皮质区域越接近，它们的转录组越相似。这种可免费访问的在线数据资源为正常和异常人脑功能的神经遗传学研究形成了高分辨率转录基线。
Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
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