Abstract
We have established and efficient system to specify NG2/PDGF-Rα/OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at low, physiological (3%) oxygen levels. This was achieved via both forebrain and spinal cord origins, with up to 98% of cells expressing NG2. Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction via ventral forebrain pathways. The OPCs mature in vitro to express O4 (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic protein-positive (MBP+) multibranching oligodendrocytes. These were cultured alongside hESC-derived neurons. The electrophysiological properties of human OPCs are similar to those of rat OPCs, with large voltage-gated sodium currents and the ability to fire action potentials. Exposure to a selective retinoid X receptor agonist increased the proportion of O4+ oligodendrocytes that express MBP from 5% to 30%. Thus, we have established a developmentally engineered system to investigate the biological properties of human OPCs and test the effects of putative remyelinating agents prior to clinical application.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Lineage*
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Cells, Cultured
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Embryonic Stem Cells / cytology*
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Embryonic Stem Cells / drug effects
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Embryonic Stem Cells / metabolism
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Fibroblast Growth Factor 2 / pharmacology
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Galactosylceramides / metabolism
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Humans
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Myelin Basic Protein / genetics
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Myelin Basic Protein / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Stem Cells / cytology*
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Neural Stem Cells / drug effects
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Neural Stem Cells / metabolism
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Neural Stem Cells / physiology
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Neurogenesis*
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / cytology*
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Oligodendroglia / drug effects
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Oligodendroglia / metabolism
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Oligodendroglia / physiology
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Oxygen / pharmacology*
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Prosencephalon / cytology
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Retinoid X Receptors / antagonists & inhibitors
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Sodium / metabolism
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Spinal Cord / cytology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Galactosylceramides
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Myelin Basic Protein
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Nerve Tissue Proteins
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OLIG2 protein, human
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Oligodendrocyte Transcription Factor 2
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Retinoid X Receptors
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galactocerebroside
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Fibroblast Growth Factor 2
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Sodium
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Oxygen