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Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays G1/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo

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    0350109 - UEM-P 2011 RIV US eng J - Journal Article
    Borghese, L. - Doležalová, Dáša - Opitz, T. - Haupt, S. - Leinhaas, A. - Steinfarz, B. - Koch, P. - Edenhofer, F. - Hampl, Aleš - Brüstle, O.
    Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays G1/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo.
    Stem Cells. Roč. 28, č. 5 (2010), s. 955-964 ISSN 1066-5099
    Grant ostatní: GA MŠk(CZ) 1M0538; EC FP6 project ESTOOLS(XE) LSHG-CT-2006-018739; EC FP7 project NeuroStemcell(XE) HEALTH-2007-B-22943
    Program: 1M
    Institutional research plan: CEZ:AV0Z50390703
    Keywords : neural stem cells * notch * neuron
    Subject RIV: EB - Genetics ; Molecular Biology
    Impact factor: 7.871, year: 2010

    The controlled in vitro differentiation of human embryonic stem cells (hESCs) and other pluripotent stem cells provides interesting prospects for generating large numbers of human neurons for a variety of biomedical applications. A major bottleneck associated with this approach is the long time required for hESC-derived neural cells (hESNSCs) to give rise to functional neuronal progeny. Here we assessed the expression of Notch pathway components in hESNSCs and demonstrate that Notch signaling is active under self-renewing culture conditions. Combined with growth factor withdrawal, inhibition of Notch signaling results in a marked acceleration of differentiation, thereby shortening the time required for the generation of electrophysiologically active hESNSC-derived neurons.
    Permanent Link: http://hdl.handle.net/11104/0190195