Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage
Yechiel Elkabetz,Georgia Panagiotakos,George Al Shamy,Nicholas D. Socci,Viviane Tabar,Lorenz Studer +5 more
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TLDR
It is proposed that R-NSCs represent the first characterized NSC stage capable of responding to patterning cues that direct differentiation toward region-specific neuronal fates, and offer new tools for harnessing the differentiation potential of human ESCs.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.read more
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Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Stuart M. Chambers,Christopher A. Fasano,Eirini P. Papapetrou,Mark J. Tomishima,Michel Sadelain,Lorenz Studer +5 more
TL;DR: Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
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The glial nature of embryonic and adult neural stem cells
TL;DR: The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated.
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Organogenesis in a dish: modeling development and disease using organoid technologies.
TL;DR: These studies illustrated two key events in structural organization during organogenesis: cell sorting out and spatially restricted lineage commitment, which are recapitulated in organoids, which self-assemble to form the cellular organization of the organ itself.
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Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease
Sonja Kriks,Jae-Won Shim,Jinghua Piao,Yosif Ganat,Dustin R. Wakeman,Zhi-Zhong Xie,Luis Carrillo-Reid,Gordon Auyeung,Chris Antonacci,Amanda Buch,Lichuan Yang,M. Flint Beal,D. James Surmeier,Jeffrey H. Kordower,Viviane Tabar,Lorenz Studer +15 more
TL;DR: A novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo is presented, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells.
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Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors
Frank Soldner,Dirk Hockemeyer,Caroline Beard,Qing Gao,George W. Bell,Elizabeth G. Cook,Gunnar Hargus,Alexandra Blak,Oliver Cooper,Maisam Mitalipova,Ole Isacson,Rudolf Jaenisch +11 more
TL;DR: In this paper, the authors showed that fibroblasts from five patients with idiopathic Parkinson's disease can be efficiently reprogrammed and subsequently differentiated into dopaminergic neurons using Cre-recombinase excisable viruses.
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