Journal
STEM CELL REPORTS
Volume 1, Issue 5, Pages 437-450Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2013.09.006
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Funding
- Multiple Sclerosis Society UK
- Evelyn Trust
- Medical Research Council
- Wellcome Trust
- National Institute for Health Research (Cambridge Biomedical Research Centre)
- Sir David Walker Fellowship
- joint Medical Research Council
- Multiple Sclerosis Society Clinical Research Training Fellowship [G0800487]
- Raymond and Beverly Sackler Studentship
- MRC [G0800487] Funding Source: UKRI
- Medical Research Council [G0800487] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10335] Funding Source: researchfish
- Rosetrees Trust [M144] Funding Source: researchfish
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We have established and efficient system to specify NG2/PDGF-R alpha/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.
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