Differentiation of Human Embryonic Stem Cells to Neural Progenitors
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Graphical Abstract
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Abstract
Human embryonic stem cells (hES), derived from the inner cell mass of the pre-implantation embryo, may serve as a valuable experimental tool for early human neurogenesis, due to their capacity for multipotency and self-renewal. They may also provide an unlimited cell source for cell replacement therapy. Neural progenitors differentiated from hES cells have considerable therapeutic potential for use in drug screening studies, or cell-based therapies for neurodegenerative diseases, because of their ability to generate defined neuronal cell types. However, for clinical application, generating a highly purified and homologous population of neural progenitors from hES cells without contamination remains a challenge. In this study, we identified an adherent culture system for efficiently differentiating neural progenitors from hES cells, cultured on homogenous feeder layers. These neural progenitors can differentiate into neurons, astrocytes and oligodendrocytes. During prolonged propagation, similar to in vivo embryonic neural progenitors, the differentiation potential of the neural progenitors shifts from neuronal to glial fate. We demonstrated that the proneural transcription factor neurogenein2 (Ngn2), and the basic helix-loop-helix transcription factor Olig2, are critical to the transition from neurogenesis to gliogenesis. Therefore, neural progenitors derived from hES cells can mimic the developmental pattern of the central nervous system and provide options for regeneration medicine.
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