Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency
(2013) In The Journal of Neuroscience : the official journal of the Society for Neuroscience 33(30). p.22-12407- 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).... (More)
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.
(Less)
- author
- publishing date
- 2013-07-24
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Brain Tissue Transplantation/methods, Cell Culture Techniques/methods, Cell Differentiation, Cell Line, Cell Lineage, Cell Proliferation/drug effects, Cerebellum/cytology, Coculture Techniques, Embryonic Stem Cells/cytology, Epidermal Growth Factor/pharmacology, Feeder Cells, Female, Fetus/cytology, Fibroblast Growth Factor 2/pharmacology, Humans, Male, Mice, Neural Stem Cells/cytology, Neuroepithelial Cells/cytology, Primary Cell Culture, Rats, Rats, Sprague-Dawley, Rhombencephalon/cytology, Stem Cell Transplantation/methods
- in
- The Journal of Neuroscience : the official journal of the Society for Neuroscience
- volume
- 33
- issue
- 30
- pages
- 16 pages
- publisher
- Society for Neuroscience
- external identifiers
-
- scopus:84880620666
- pmid:23884946
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.0130-13.2013
- language
- English
- LU publication?
- no
- id
- 1b7222ee-dcd2-4a43-84c4-dd3971f78e96
- date added to LUP
- 2021-08-10 13:29:53
- date last changed
- 2024-01-05 13:53:25
@article{1b7222ee-dcd2-4a43-84c4-dd3971f78e96,
abstract = {{<p>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. </p>}},
author = {{Tailor, Jignesh and Kittappa, Raja and Leto, Ketty and Gates, Monte and Borel, Melodie and Paulsen, Ole and Spitzer, Sonia and Karadottir, Ragnhildur Thora and Rossi, Ferdinando and Falk, Anna and Smith, Austin}},
issn = {{1529-2401}},
keywords = {{Animals; Brain Tissue Transplantation/methods; Cell Culture Techniques/methods; Cell Differentiation; Cell Line; Cell Lineage; Cell Proliferation/drug effects; Cerebellum/cytology; Coculture Techniques; Embryonic Stem Cells/cytology; Epidermal Growth Factor/pharmacology; Feeder Cells; Female; Fetus/cytology; Fibroblast Growth Factor 2/pharmacology; Humans; Male; Mice; Neural Stem Cells/cytology; Neuroepithelial Cells/cytology; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Rhombencephalon/cytology; Stem Cell Transplantation/methods}},
language = {{eng}},
month = {{07}},
number = {{30}},
pages = {{22--12407}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience : the official journal of the Society for Neuroscience}},
title = {{Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency}},
url = {{https://lup.lub.lu.se/search/files/101076707/Stem_Cells_Expanded_from_the_Human.pdf}},
doi = {{10.1523/JNEUROSCI.0130-13.2013}},
volume = {{33}},
year = {{2013}},
}