Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells.
BACKGROUND
Directed differentiation of human induced pluripotent stem cells (hiPSC) into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation.


RESULTS
We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE) cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC) in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons.


CONCLUSIONS
Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders.
Zeng
Hui
H
Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
Guo
Min
M
Martins-Taylor
Kristen
K
Wang
Xiaofang
X
Zhang
Zheng
Z
Park
Jung Woo
JW
Zhan
Shuning
S
Kronenberg
Mark S
MS
Lichtler
Alexander
A
Liu
Hui-Xia
HX
Chen
Fang-Ping
FP
Yue
Lixia
L
Li
Xue-Jun
XJ
Xu
Ren-He
RH
D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018698:Glutamic Acid