Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA; Department of Computer Science, College of Computing and Information, State University of New York, Albany, NY 12144, USA.
Neuron. 2014 Jul 2;83(1):51-68. doi: 10.1016/j.neuron.2014.05.013.
Many neurological and psychiatric disorders affect the cerebral cortex, and a clearer understanding of the molecular processes underlying human corticogenesis will provide greater insight into such pathologies. To date, knowledge of gene expression changes accompanying corticogenesis is largely based on murine data. Here we present a searchable, comprehensive, temporal gene expression data set encompassing cerebral cortical development from human embryonic stem cells (hESCs). Using a modified differentiation protocol that yields neurons suggestive of prefrontal cortex, we identified sets of genes and long noncoding RNAs that significantly change during corticogenesis and those enriched for disease-associations. Numerous alternatively spliced genes with varying temporal patterns of expression are revealed, including TGIF1, involved in holoprosencephaly, and MARK1, involved in autism. We have created a database (http://cortecon.neuralsci.org/) that provides online, query-based access to changes in RNA expression and alternatively spliced transcripts during human cortical development.
许多神经和精神疾病都会影响大脑皮层,而更深入地了解人类皮质发生的分子过程将有助于深入了解这些病理。迄今为止,伴随皮质发生的基因表达变化的知识在很大程度上基于鼠类数据。在这里,我们展示了一个可搜索的、全面的、时间性的基因表达数据集,涵盖了人类胚胎干细胞(hESC)的大脑皮质发育过程。使用一种改良的分化方案,该方案产生了类似于前额叶皮层的神经元,我们鉴定了在皮质发生过程中显著变化的基因和长非编码 RNA 集,以及那些与疾病相关的基因和长非编码 RNA 集。揭示了许多具有不同时间表达模式的选择性剪接基因,包括涉及前脑无裂畸形的 TGIF1 和涉及自闭症的 MARK1。我们创建了一个数据库(http://cortecon.neuralsci.org/),该数据库提供了在线查询访问功能,可查询人类皮质发育过程中 RNA 表达和选择性剪接转录本的变化。