Developmental regulation of human cortex transcription and its clinical relevance at single base resolution.
Developmental regulation of human cortex transcription and its clinical relevance at single base resolution.
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DOI：
10.1038/nn.3898
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发表时间：
2015-01
影响因子：
25
通讯作者：
Weinberger, Daniel R.
中科院分区：
文献类型：
--
作者：
Jaffe, Andrew E.;Shin, Jooheon;Collado-Torres, Leonardo;Leek, Jeffrey T.;Tao, Ran;Li, Chao;Gao, Yuan;Jia, Yankai;Maher, Brady J.;Hyde, Thomas M.;Kleinman, Joel E.;Weinberger, Daniel R.
对人脑的转录组分析提供了关于发育和疾病的基本见解，但在很大程度上依赖于现有的注释。我们对六个生命阶段的72个前额叶皮质样本的转录本进行了测序，并确定了与发育和衰老相关的50,650个差异表达区域(DER)，这些区域与注释无关。虽然许多DERs被注释为非外显子序列(41.1%)，但大多数DERs在从独立样本中提取的胞质mRNA中受到类似的调控。DERs在16个大脑区域和发育中的小鼠皮质中发育保守，并在不同类型的细胞和组织中表达。DER进一步丰富了活跃的染色质标记和精神分裂症等神经发育障碍的临床风险。最后，我们定量地证明了这些DER与与分化和成熟相关的神经元表型的变化有关。这些数据突出了大脑发育过程中转录动力学的保守分子签名，一些潜在的临床相关性，以及人类大脑转录组的不完整注释。
Transcriptome analysis of human brain provides fundamental insight about development and disease, but largely relies on existing annotation. We sequenced transcriptomes of 72 prefrontal cortex samples across six life stages, and identified 50,650 differentially expression regions (DERs) associated with developmental and aging, agnostic of annotation. While many DERs annotated to non-exonic sequence (41.1%), most were similarly regulated in cytosolic mRNA extracted from independent samples. The DERs were developmentally conserved across 16 brain regions and within the developing mouse cortex, and were expressed in diverse cell and tissue types. The DERs were further enriched for active chromatin marks and clinical risk for neurodevelopmental disorders like schizophrenia. Lastly, we demonstrate quantitatively that these DERs associate with a changing neuronal phenotype related to differentiation and maturation. These data highlight conserved molecular signatures of transcriptional dynamics across brain development, some potential clinical relevance and the incomplete annotation of the human brain transcriptome.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
14.9
作者：
Hansen KD;Brenner SE;Dudoit S
通讯作者：
Dudoit S
影响因子：
14.9
作者：
Hupe M;Li MX;Gertow Gillner K;Adams RH;Stenman JM
通讯作者：
Stenman JM
影响因子：
64.8
作者：
Frankland, PW;O'Brien, C;Silva, AJ
通讯作者：
Silva, AJ