Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells

Abstract

Myelin-related disorders such as multiple sclerosis and leukodystrophies, where restoration of oligodendrocyte function would provide an effective treatment, are poised to benefit greatly from stem cell biology. Progress in myelin repair has been constrained by difficulties in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but current differentiation strategies are poorly reproducible and generate heterogenous populations of cells. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes in vitro and in vivo. Our results demonstrate that mouse pluripotent stem cells provide a pure population of myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development and drug screening.

Cited2 Gene Controls Pluripotency and Cardiomyocyte Differentiation of Murine Embryonic Stem Cells through Oct4 Gene

“…Neuronal differentiation was carried out as described previously (36). In brief, 2 ϫ 10 5 ES cells were seeded on ultra low cluster plates (Costar) in EpiSC basal medium and 100 ng/ml Noggin (R&D Systems).…”

“…Immunostaining of ESC-induced neuronal cells was performed as described previously (36). ␤-III Tublin antibody (Covance) and Alexa-488-conjugated antibody (Molecular Probes) were used as primary and secondary antibodies, respectively.…”

Inhibition of TROY Promotes OPC Differentiation and Increases Therapeutic Efficacy of OPC Graft for Spinal Cord Injury

“…OPCs only constitute 5% of total cells in adult brain and the primary OPCs are not readily available [1,49]. Moreover, the derivation of engraftable OPCs from pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, has proven slow and tedious [49][50][51][52]. Accordingly, effective in vitro expansion of OPCs is essential for successful graft treatment.…”

Depletion of Olig2 in oligodendrocyte progenitor cells infected by Theiler’s murine encephalomyelitis virus

“…Recent advances in pluripotent stem cell and reprogramming technologies have enabled production of pure populations of oligodendrocyte progenitor cells (OPCs) in vitro (Najm et al 2011b. These in vitro-generated OPCs accurately reflect the molecular, cellular, and functional properties of OPCs in vivo.…”