title: Modeling human cortical development in vitro using induced pluripotent stem cells.
abstract: Human induced pluripotent stem cells (hiPSCs) are emerging as a tool for understanding human brain development at cellular, molecular, and genomic levels. Here we show that hiPSCs grown in suspension in the presence of rostral neuralizing factors can generate 3D structures containing polarized radial glia, intermediate progenitors, and a spectrum of layer-specific cortical neurons reminiscent of their organization in vivo. The hiPSC-derived multilayered structures express a gene expression profile typical of the embryonic telencephalon but not that of other CNS regions. Their transcriptome is highly enriched in transcription factors controlling the specification, growth, and patterning of the dorsal telencephalon and displays highest correlation with that of the early human cerebral cortical wall at 8-10 wk after conception. Thus, hiPSC are capable of enacting a transcriptional program specifying human telencephalic (pallial) development. This model will allow the study of human brain development as well as disorders of the human cerebral cortex.
authors: Program in Neurodevelopment and Regeneration, Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Jessica
authors: J
authors: Mariani
authors: Maria Vittoria
authors: MV
authors: Simonini
authors: Dean
authors: D
authors: Palejev
authors: Livia
authors: L
authors: Tomasini
authors: Gianfilippo
authors: G
authors: Coppola
authors: Anna M
authors: AM
authors: Szekely
authors: Tamas L
authors: TL
authors: Horvath
authors: Flora M
authors: FM
authors: Vaccarino
mesh_terms: D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D014157:Transcription Factors