Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage
Open accessAbstract
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.
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Ectopic production of TH and a subsequent increase in catecholamine synthesis agrees with findings from valproic-acid based models of ASD and postmortem studies of patients with schizophrenia.
“Ectopic production of TH and a subsequent increase in catecholamine synthesis agrees with findings from valproic-acid based models of ASD33 and postmortem studies of patients with schizophrenia34.”
From Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome (2011) · cites this paper as [34]
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- Authors
- Elkabetz, Y., Panagiotakos, G., Al Shamy, G., Socci, N. D., Tabar, V., & Studer, L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-01-15
- Volume
- 22
- Issue
- 2
- Pages
- 152-165
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2192751
- OpenAlex
- W2152069828
- Cited by
- 677
- References
- 58
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 17 · 2023: 20 · 2022: 32 · 2021: 33 · 2020: 53 · 2019: 43 · 2018: 37 · 2017: 32 · 2016: 38 · 2015: 28 · 2014: 44 · 2013: 48 · 2012: 56
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Starr Foundation
- Kinetics Foundation
- National Science Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neural rosettes, neural stem cells, human embryonic stem cells, neuronal differentiation, Sonic hedgehog signaling, Notch signaling, neural plate, clonal isolation
- MeSH terms
- Animals, Cell Differentiation, Humans, Neurons, Signal Transduction, Cell Lineage, Body Patterning, Pluripotent Stem Cells, Neuroepithelial Cells, Mice, Receptors, Notch, Embryonic Stem Cells, Hedgehog Proteins, Neural Plate
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