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


ABSTRACT: Stem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. 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 both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies. 6 total samples were analyzed. Pluripotent epiblast stem cells (EpiSCs) were differentiated to patterned neural rosettes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes. OPCs and oligodedrocytes were analyzed at two separate passages (3 and 11).

ORGANISM(S): Mus musculus

SUBMITTER: Paul Tesar 

PROVIDER: E-GEOD-31562 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Najm Fadi J FJ   Zaremba Anita A   Caprariello Andrew V AV   Nayak Shreya S   Freundt Eric C EC   Scacheri Peter C PC   Miller Robert H RH   Tesar Paul J PJ  

Nature methods 20110925 11


Myelin-related disorders such as multiple sclerosis and leukodystrophies, for which restoration of oligodendrocyte function would be 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 re  ...[more]

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