title: High yields of oligodendrocyte lineage cells from human embryonic stem cells at physiological oxygen tensions for evaluation of translational biology.
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.
authors.affiliation: Department of Clinical Neurosciences, Cambridge University, Cambridge CB2 0PY, UK ; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, Cambridge University, Cambridge CB3 0ES, UK.
authors.forename: Sybil R L
authors.initials: SR
authors.lastname: Stacpoole
authors.forename: Sonia
authors.initials: S
authors.lastname: Spitzer
authors.forename: Bilada
authors.initials: B
authors.lastname: Bilican
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: Ragnhildur
authors.initials: R
authors.lastname: Karadottir
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000200:Action Potentials; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005699:Galactosylceramides / Q000378:metabolism; D006801:Humans; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D016548:Prosencephalon / Q000166:cytology; D047488:Retinoid X Receptors / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D005699:Galactosylceramides; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D010100:Oxygen; D047488:Retinoid X Receptors; D012964:Sodium; C405708:OLIG2 protein, human; C002454:galactocerebroside