Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage.

By Yechiel Elkabetz, Georgia Panagiotakos, George Al Shamy, Nicholas D. Socci, V. Tabar, L. Studer. Genes & Development, 2008

703 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3d88c7e728e94278a2f3ef654818a5e93d937743

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Citations in the corpus

Modeling early retinal development with human embryonic and induced pluripotent stem cells (2009, background): “Previous reports have demonstrated that hESC-derived neuroectodermal cells will adopt anterior neuroepithelial characteristics in the absence of exogenous signaling molecules (14, 15).”
Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses (2012, background): “Human ES cell–derived neural stem cells form rosette structures following neural inductio”
Floor plate-derived dopamine neurons from hESCs efficiently engraft in animal models of PD (2011, background): “There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowt”
The Glial Nature of Embryonic and Adult Neural Stem Cells (2009, background): “INM may be a cell-autonomous feature of neuroepithelial or RG-like cells because NSCs derived from embryonic stem cell lines both express RG markers and undergo nucleokinesis as they progress through the cell cycle (Conti et al. 2005, Glaser & Brustle 2005, Elkabetz et al. 2008).”
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling (2009, methodology): “has similar neural-inducing properties, and treatment with recombinant Noggin has been used in several hES-cell neural induction protocol”
Organogenesis in a dish: Modeling development and disease using organoid technologies (2014, background): “Brain Embryonic chick brain cells (45) Neural rosettes from mouse and human PSCs (48, 49) Cerebral organoids from mouse and human PSCs (28, 55) Pituitary Chick anterior pituitary (115) None Adenohypophysis organoids from mouse PSCs (73) Mammary gland Mammary gland from adult virgin mice (75) None 3D”
Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors (2009, methodology): “Generation of Dopaminergic Neurons from PD Patient-Derived hiPSCs Several protocols for the directed differentiation of hESCs into dopaminergic neurons have been established (Elkabetz et al., 2008; Kim et al., 2006; Perrier et al., 2004; Roy et al., 2006; Sonntag et al., 2007).”