Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage Journal Article
| Authors: | Elkabetz, Y.; Panagiotakos, G.; Al Shamy, G.; Socci, N. D.; Tabar, V.; Studer, L. |
| Article Title: | Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage |
| Abstract: | 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. © 2008 by Cold Spring Harbor Laboratory Press. |
| Keywords: | signal transduction; human cell; animals; mice; embryonic stem cell; hedgehog proteins; cell fate; neural stem cell; cell differentiation; neurons; cell lineage; engraftment; receptors, notch; cell isolation; embryonic stem cells; rosette formation; pluripotent stem cells; neural stem cells; body patterning; neuroectoderm; neural plate; human embryonic stem cells; neuroepithelial cells; neural patterning; neuronal specification |
| Journal Title: | Genes and Development |
| Volume: | 22 |
| Issue: | 2 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2008-01-15 |
| Start Page: | 152 |
| End Page: | 165 |
| Language: | English |
| DOI: | 10.1101/gad.1616208 |
| PUBMED: | 18198334 |
| PROVIDER: | scopus |
| PMCID: | PMC2192751 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 108" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Source: Scopus" |
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