Spatial-temporal transcriptional dynamics of long non-coding RNAs in human brain
Spatial-temporal transcriptional dynamics of long non-coding RNAs in human brain
复制标题
人脑中长非编码RNA的时空转录动力学
DOI：
10.1093/hmg/ddx203
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发表时间：
2017-08
影响因子：
3.5
通讯作者：
Yang Jian-Hua
中科院分区：
文献类型：
--
作者：
Zhang Xiao-Qin;Wang Ze-Lin;Poon Ming-Wai;Yang Jian-Hua
人脑的功能结构在很大程度上取决于转录过程的时间和空间调节。然而，人类大脑发育过程中长非编码RNA(LncRNAs)的时空转录格局仍然知之甚少。在这里，我们报告了从早期胚胎发育到成年后期的16个区域收集的1340份死后人脑标本的全基因组LncRNA转录分析。我们发现，lncRNA转录组在胎儿发育过程中发生了戏剧性的变化，但在出生后一直过渡到令人惊讶的相对稳定状态，直到成年后期。我们还发现，lncRNAs的转录图谱在空间上是不同的，这种空间差异是发育调节的。在所研究的16个大脑区域(小脑皮质、丘脑、纹状体、杏仁核、海马体和11个新皮质区域)中，小脑皮质在整个发育过程中显示出最明显的其余大脑区域的lncRNA表达特征，反映了其独特的发育和功能特征。此外，通过对时空动态lncRNAs的功能模块和细胞过程的表征，我们发现它们与RNA加工、神经元分化和突触信号传递过程密切相关。此外，我们还发现，许多与神经退行性阿尔茨海默病和帕金森病相关的lncRNAs在人脑的胚胎发育过程中共表达，并影响到趋同的生物学过程。总之，我们的研究为人类大脑发育中的lncRNA转录动力学提供了一个全面的图谱，这可能有助于理解人类大脑功能和疾病的分子基础。
The functional architecture of the human brain is greatly determined by the temporal and spatial regulation of the transcription process. However, the spatial and temporal transcriptional landscape of long non-coding RNAs (lncRNAs) during human brain development remains poorly understood. Here, we report the genome-wide lncRNA transcriptional analysis in an extensive series of 1340 post-mortem human brain specimens collected from 16 regions spanning the period from early embryo development to late adulthood. We discovered that lncRNA transcriptome dramatically changed during fetal development, while transited to a surprisingly relatively stable state after birth till the late adulthood. We also discovered that the transcription map of lncRNAs was spatially different, and that this spatial difference was developmentally regulated. Of the 16 brain regions explored (cerebellar cortex, thalamus, striatum, amygdala, hippocampus and 11 neocortex areas), cerebellar cortex showed the most distinct lncRNA expression features from all remaining brain regions throughout the whole developmental period, reflecting its unique developmental and functional features. Furthermore, by characterizing the functional modules and cellular processes of the spatial-temporal dynamic lncRNAs, we found that they were significantly associated with the RNA processing, neuron differentiation and synaptic signal transportation processes. Furthermore, we found that many lncRNAs associated with the neurodegenerative Alzheimer and Parkinson diseases were co-expressed in the fetal development of the human brain, and affected the convergent biological processes. In summary, our study provides a comprehensive map for lncRNA transcription dynamics in human brain development, which might shed light on the understanding of the molecular underpinnings of human brain function and disease.
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影响因子：
--
作者：
I. Ozturk;H. Orhan;Z. Dogan
通讯作者：
I. Ozturk;H. Orhan;Z. Dogan
影响因子：
4.6
作者：
D'haene E;Jacobs EZ;Volders PJ;De Meyer T;Menten B;Vergult S
通讯作者：
Vergult S
DOI：
--
发表时间：
1996
期刊：
--
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Hu Z;Hung JH;Wang Y;Chang YC;Huang CL;Huyck M;DeLisi C
通讯作者：
DeLisi C
影响因子：
2.4
作者：
Mercer TR;Qureshi IA;Gokhan S;Dinger ME;Li G;Mattick JS;Mehler MF
通讯作者：
Mehler MF