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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2966874
- author
- 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
- organization
- publishing date
- 2012
- 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
- 2016-04-01 14:29:40
- date last changed
- 2022-05-15 18:44:49
@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 = {{https://lup.lub.lu.se/search/files/4006203/3635656}},
doi = {{10.1016/j.celrep.2012.04.009}},
volume = {{1}},
year = {{2012}},
}