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Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.

Tailor, J; Kittappa, R; Leto, K; Gates, M; Borel, M; Paulsen, O; Spitzer, S; ... Smith, A; + view all (2013) Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency. The Journal of Neuroscience , 33 (30) 12407 -12422. 10.1523/JNEUROSCI.0130-13.2013. Green open access

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Abstract

Stem cell lines that faithfully maintain the regional identity and developmental potency of progenitors in the human brain would create new opportunities in developmental neurobiology and provide a resource for generating specialized human neurons. However, to date, neural progenitor cultures derived from the human brain have either been short-lived or exhibit restricted, predominantly glial, differentiation capacity. Pluripotent stem cells are an alternative source, but to ascertain definitively the identity and fidelity of cell types generated solely in vitro is problematic. Here, we show that hindbrain neuroepithelial stem (hbNES) cells can be derived and massively expanded from early human embryos (week 5-7, Carnegie stage 15-17). These cell lines are propagated in adherent culture in the presence of EGF and FGF2 and retain progenitor characteristics, including SOX1 expression, formation of rosette-like structures, and high neurogenic capacity. They generate GABAergic, glutamatergic and, at lower frequency, serotonergic neurons. Importantly, hbNES cells stably maintain hindbrain specification and generate upper rhombic lip derivatives on exposure to bone morphogenetic protein (BMP). When grafted into neonatal rat brain, they show potential for integration into cerebellar development and produce cerebellar granule-like cells, albeit at low frequency. hbNES cells offer a new system to study human cerebellar specification and development and to model diseases of the hindbrain. They also provide a benchmark for the production of similar long-term neuroepithelial-like stem cells (lt-NES) from pluripotent cell lines. To our knowledge, hbNES cells are the first demonstration of highly expandable neuroepithelial stem cells derived from the human embryo without genetic immortalization.

Type: Article
Title: Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.0130-13.2013
Publisher version: http://dx.doi.org/10.1523/JNEUROSCI.0130-13.2013
Language: English
Additional information: Copyright © 2013 the authors Available for non-commercial purposes under the terms of the Creative Commons Attribution - Noncommercial - Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0). PMCID: PMC3721847
Keywords: Animals, Brain Tissue Transplantation, Cell Culture Techniques, Cell Differentiation, Cell Line, Cell Lineage, Cell Proliferation, Cerebellum, Coculture Techniques, Embryonic Stem Cells, Epidermal Growth Factor, Feeder Cells, Female, Fetus, Fibroblast Growth Factor 2, Humans, Male, Mice, Neural Stem Cells, Neuroepithelial Cells, Primary Cell Culture, Rats, Rats, Sprague-Dawley, Rhombencephalon, Stem Cell Transplantation
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 Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1420441
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