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.
|Number of pages||14|
|Journal||Stem Cell Reports|
|Publication status||Published - 19 Nov 2013|
Bibliographical noteFunding Information:
This work was supported by the Multiple Sclerosis Society UK, the Evelyn Trust, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (Cambridge Biomedical Research Centre). S.R.L.S. was supported by a Sir David Walker Fellowship, a joint Medical Research Council and Multiple Sclerosis Society Clinical Research Training Fellowship (No. G0800487), and a Raymond and Beverly Sackler Studentship.