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Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions.

Kirkeby, Agnete LU ; Grealish, Shane LU ; Wolf, Daniel LU ; Nelander Wahlestedt, Jenny LU ; Wood, James LU ; Lundblad, Martin LU ; Lindvall, Olle LU and Parmar, Malin LU (2012) In Cell Reports 1(6). p.703-714
Abstract
To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain... (More)
To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM) identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
1
issue
6
pages
703 - 714
publisher
Cell Press
external identifiers
  • wos:000309713100014
  • pmid:22813745
  • scopus:84863094725
ISSN
2211-1247
DOI
10.1016/j.celrep.2012.04.009
language
English
LU publication?
yes
id
db837d37-b230-4321-9c75-046218c33e10 (old id 2966874)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22813745?dopt=Abstract
date added to LUP
2012-08-09 20:20:44
date last changed
2017-11-19 03:56:55
@article{db837d37-b230-4321-9c75-046218c33e10,
  abstract     = {To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM) identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.},
  author       = {Kirkeby, Agnete and Grealish, Shane and Wolf, Daniel and Nelander Wahlestedt, Jenny and Wood, James and Lundblad, Martin and Lindvall, Olle and Parmar, Malin},
  issn         = {2211-1247},
  language     = {eng},
  number       = {6},
  pages        = {703--714},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions.},
  url          = {http://dx.doi.org/10.1016/j.celrep.2012.04.009},
  volume       = {1},
  year         = {2012},
}