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Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons.

Falk, A; Koch, P; Kesavan, J; Takashima, Y; Ladewig, J; Alexander, M; Wiskow, O; ... Brüstle, O; + view all (2012) Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons. PLOS One , 7 (1) , Article e29597. 10.1371/journal.pone.0029597. Green open access

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Abstract

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds.

Type: Article
Title: Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0029597
Publisher version: http://dx.doi.org/10.1371/journal.pone.0029597
Language: English
Additional information: © 2012 Falk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the European Commission (http://cordis.europa.eu/; LSHG-CT-2006-018739, ESTOOLS; grant 222943, Neurostemcell; LSHB-CT-2007-037766, Neuroscreen), the UK Medical Research Council (http://www.mrc.ac.uk), the German Research Foundation (DFG; http://www.dfg.de/; SFB-TR3), the German Federal Ministry for Education and Research (BMBF; http://www.bmbf.de/; grant 01GNO813), the Stem Cell Network North Rhine Westphalia (http://www.stammzellen.nrw.de/; L-072.0055) and the Hertie Foundation (http://www.ghst.de/). AF was supported by the Swedish Research Council (http://www.vr.se) and the Swedish Hjärnfonden (http://www.hjarnfonden.se) and YT by an EMBO Long-Term Fellowship (http://www.embo.org). JT is a National Institute of Health Research (NIHR) Clinical Research Training Fellow (http://www.nihr.ac.uk) and a Raymond and Beverly Sackler Fellow (http://www.medschl.cam.ac.uk) and AS is a Medical Research Council Professor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Cell Differentiation, Cell Line, Cell Proliferation, Cluster Analysis, Epidermal Growth Factor, Fibroblast Growth Factor 2, Fluorescent Antibody Technique, Gene Expression Profiling, Humans, Induced Pluripotent Stem Cells, Neural Stem Cells, Neuroepithelial Cells, Neuroglia, Neurons, Oligonucleotide Array Sequence Analysis, Pluripotent Stem Cells, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1362504
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