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Yechiel Elkabetz1,2, Georgia Panagiotakos2, George Al Shamy2, Nicholas D. Socci3, Viviane Tabar2, and Lorenz Studer1,2,4
1 Developmental Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA; 2 Division of Neurosurgery, Sloan-Kettering Institute, New York, New York 10021, USA; 3 Computational Biology Center, Sloan-Kettering Institute, New York, New York 10021, USA
Neural stem cells (NSCs) yield both neuronal and glial progeny, but their differentiation potential toward multiple region-specific neuron types remains remarkably poor. In contrast, embryonic stem cell (ESC) progeny readily yield region-specific neuronal fates in response to appropriate developmental signals. Here we demonstrate prospective and clonal isolation of neural rosette cells (termed R-NSCs), a novel NSC type with broad differentiation potential toward CNS and PNS fates and capable of in vivo engraftment. R-NSCs can be derived from human and mouse ESCs or from neural plate stage embryos. While R-NSCs express markers classically associated with NSC fate, we identified a set of genes that specifically mark the R-NSC state. Maintenance of R-NSCs is promoted by activation of SHH and Notch pathways. In the absence of these signals, R-NSCs rapidly lose rosette organization and progress to a more restricted NSC stage. We propose that R-NSCs represent the first characterized NSC stage capable of responding to patterning cues that direct differentiation toward region-specific neuronal fates. In addition, the R-NSC-specific genetic markers presented here offer new tools for harnessing the differentiation potential of human ESCs.
[Keywords: Human embryonic stem cells; neural patterning; neural stem cells; neuronal specification]]
Received September 17, 2007; revised version accepted November 21, 2007.
4 Corresponding author.
