| Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. | |
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MedLine Citation:
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PMID: 22306606 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Efforts to study the development and function of the human cerebral cortex in health and disease have been limited by the availability of model systems. Extrapolating from our understanding of rodent cortical development, we have developed a robust, multistep process for human cortical development from pluripotent stem cells: directed differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells to cortical stem and progenitor cells, followed by an extended period of cortical neurogenesis, neuronal terminal differentiation to acquire mature electrophysiological properties, and functional excitatory synaptic network formation. We found that induction of cortical neuroepithelial stem cells from human ES cells and human iPS cells was dependent on retinoid signaling. Furthermore, human ES cell and iPS cell differentiation to cerebral cortex recapitulated in vivo development to generate all classes of cortical projection neurons in a fixed temporal order. This system enables functional studies of human cerebral cortex development and the generation of individual-specific cortical networks ex vivo for disease modeling and therapeutic purposes. |
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Authors:
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Yichen Shi; Peter Kirwan; James Smith; Hugh P C Robinson; Frederick J Livesey |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-02-05 |
Journal Detail:
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Title: Nature neuroscience Volume: 15 ISSN: 1546-1726 ISO Abbreviation: Nat. Neurosci. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-24 Completed Date: 2012-04-18 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 9809671 Medline TA: Nat Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 477-86, S1 Citation Subset: IM |
Affiliation:
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Gurdon Institute, University of Cambridge, Cambridge, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Cyano-7-nitroquinoxaline-2,3-dione
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pharmacology Cell Differentiation / drug effects, physiology Cell Line Cells, Cultured Cerebral Cortex / cytology*, embryology* Embryonic Stem Cells / cytology*, physiology Excitatory Amino Acid Antagonists / pharmacology Fetus Gene Expression Regulation, Developmental / drug effects Glutamic Acid / pharmacology Humans Intracellular Signaling Peptides and Proteins / metabolism Ki-67 Antigen / metabolism Membrane Proteins / metabolism Nerve Tissue Proteins / genetics, metabolism Neurogenesis / physiology* Patch-Clamp Techniques Piperidines / pharmacology Pluripotent Stem Cells / cytology*, drug effects, physiology Potassium Channel Blockers / pharmacology RNA, Messenger Retinoids / pharmacology Signal Transduction / drug effects Sodium Channel Blockers / pharmacology Synapses / drug effects, physiology* Synaptic Potentials / drug effects, physiology Tetrodotoxin / pharmacology Time Factors Transcription Factors / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/4-aminopiperidine; 0/DLG4 protein, human; 0/Excitatory Amino Acid Antagonists; 0/Intracellular Signaling Peptides and Proteins; 0/Ki-67 Antigen; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Piperidines; 0/Potassium Channel Blockers; 0/RNA, Messenger; 0/Retinoids; 0/Sodium Channel Blockers; 0/Transcription Factors; 0/UNC13B protein, human; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 4368-28-9/Tetrodotoxin; 56-86-0/Glutamic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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