Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions. / Kirkeby, Agnete; Grealish, Shane; Wolf, Daniel A.; Nelander, Jenny; Wood, James; Lundblad, Martin; Lindvall, Olle; Parmar, Malin.
In: Cell Reports, Vol. 1, No. 6, 28.06.2012, p. 703-714.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions
AU - Kirkeby, Agnete
AU - Grealish, Shane
AU - Wolf, Daniel A.
AU - Nelander, Jenny
AU - Wood, James
AU - Lundblad, Martin
AU - Lindvall, Olle
AU - Parmar, Malin
PY - 2012/6/28
Y1 - 2012/6/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863094725&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2012.04.009
DO - 10.1016/j.celrep.2012.04.009
M3 - Journal article
C2 - 22813745
AN - SCOPUS:84863094725
VL - 1
SP - 703
EP - 714
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -
ID: 228506311