CORTECON: A Temporal Transcriptome Analysis of In Vitro Human Cerebral Cortex Development from Human Embryonic Stem Cells

• Published in: Neuron (Cambridge, Mass.) Mass.), 2014-07, Vol.83 (1), p.51-68
• Main Authors: van de Leemput, Joyce, Boles, Nathan C., Kiehl, Thomas R., Corneo, Barbara, Lederman, Patty, Menon, Vilas, Lee, Changkyu, Martinez, Refugio A., Levi, Boaz P., Thompson, Carol L., Yao, Shuyuan, Kaykas, Ajamete, Temple, Sally, Fasano, Christopher A.
• Format: Article
• Language: English
• Subjects: Acquisitions & mergers; Alzheimer's disease; Animals; Brain diseases; Cell Differentiation - genetics; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Chronic fatigue syndrome; Databases, Genetic - trends; Diabetic retinopathy; Embryonic Stem Cells - physiology; Gene expression; Gene Expression Profiling - methods; Gene Expression Profiling - trends; Gene Regulatory Networks - genetics; Humans; Mice; Neurons; Organogenesis - physiology; Schizophrenia; Stem cells; Technological change; Time Factors
• ISSN: 0896-6273; 1097-4199
• 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. •Temporal RNA-seq resource of human cortical development from hESCs•Protocol resulting in enrichment for prefrontal cortical fates•Identified genes with temporally regulated splicing during corticogenesis•Online, searchable database of temporal profile and associated disease information Using RNA-seq, van de Leemput and Boles et al. have established a resource profiling the transcriptional changes occurring during human cortical development using an in vitro model.