title: Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
abstract: Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin- and somatostatin-expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient for modeling human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.
authors: Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Ave, New York, NY 10065, USA.
authors: Asif M
authors: AM
authors: Maroof
authors: Sotirios
authors: S
authors: Keros
authors: Jennifer A
authors: JA
authors: Tyson
authors: Shui-Wang
authors: SW
authors: Ying
authors: Yosif M
authors: YM
authors: Ganat
authors: Florian T
authors: FT
authors: Merkle
authors: Becky
authors: B
authors: Liu
authors: Adam
authors: A
authors: Goulburn
authors: Edouard G
authors: EG
authors: Stanley
authors: Andrew G
authors: AG
authors: Elefanty
authors: Hans Ruedi
authors: HR
authors: Widmer
authors: Kevin
authors: K
authors: Eggan
authors: Peter A
authors: PA
authors: Goldstein
authors: Stewart A
authors: SA
authors: Anderson
authors: Lorenz
authors: L
authors: Studer
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D061252:Feeder Cells / Q000166:cytology / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051153:Wnt Proteins; D049452:Green Fluorescent Proteins
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