Zhang Xiao-Qin, Wang Ze-Lin, Poon Ming-Wai, Yang Jian-Hua
School of Medicine, South China University of Technology (SCUT), Guangzhou 510006, P. R. China.
RNA Medicine and Informatics Center, Key Laboratory of Gene Engineering of the Ministry of Education; State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
Hum Mol Genet. 2017 Aug 15;26(16):3202-3211. doi: 10.1093/hmg/ddx203.
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.
人类大脑的功能结构很大程度上由转录过程的时空调节所决定。然而，在人类大脑发育过程中，长链非编码RNA（lncRNA）的时空转录图谱仍知之甚少。在此，我们报告了对1340份死后人类大脑标本进行的全基因组lncRNA转录分析，这些标本来自16个区域，涵盖了从胚胎早期发育到成年晚期的整个阶段。我们发现，lncRNA转录组在胎儿发育期间发生了显著变化，而在出生后直至成年晚期则转变为一个令人惊讶的相对稳定状态。我们还发现，lncRNA的转录图谱在空间上存在差异，且这种空间差异受到发育调控。在探索的16个脑区（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阶段显示出与所有其他脑区最明显不同的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lncRNA的功能模块和细胞过程进行表征，我们发现它们与RNA加工、神经元分化和突触信号传递过程显著相关。此外，我们发现许多与神经退行性疾病阿尔茨海默病和帕金森病相关的lncRNA在人类大脑的胎儿发育阶段共同表达，并影响趋同的生物学过程。总之，我们的研究提供了人类大脑发育中lncRNA转录动态的综合图谱，这可能有助于深入了解人类大脑功能和疾病的分子基础。
